A perspective on the early days of RAS research
AbstractThe name of the oncogene,ras, has its origin in studies of murine leukemia viruses in the 1960s by Jenny Harvey (H-ras) and by Werner Kirsten (K-ras) which, at high doses, produced sarcomas in rats. Transforming retroviruses were isolated, and its oncogene was namedras after rat sarcoma. From 1979, cellularras sequences with transforming properties were identified by transfection of tumor DNA initially by Robert Weinberg from rodent tumors, and the isolation of homologous oncogenes from human tumors soon followed, includingHRAS andKRAS, and a new member of the family namedNRAS. I review these discoveries, placing e...
Source: Cancer and Metastasis Reviews - July 29, 2020 Category: Cancer & Oncology Source Type: research

Molecular epidemiology and diagnostics of KRAS mutations in human cancer
AbstractRAS mutation is the most frequent oncogenic alteration in human cancers. KRAS is the most frequently mutated followed by NRAS. The emblematic KRAS mutant cancers are pancreatic, colorectal, lung adenocarcinomas and urogenital cancers. KRAS mutation frequencies are relatively stable worldwide in various cancer types with the one exception of lung adenocarcinoma. The frequencies of KRAS variant alleles appears cancer type specific, reflecting the various carcinogenic processes. In addition to point mutation KRAS, allelic imbalances are also frequent in human cancers leading to the predominance of a mutant allele. KRA...
Source: Cancer and Metastasis Reviews - July 29, 2020 Category: Cancer & Oncology Source Type: research

Structure-based inhibitor design of mutant RAS proteins —a paradigm shift
AbstractAs a member of small GTPase family, KRAS protein is a key physiological modulator of various cellular activities including proliferation. However, mutations of KRAS present in numerous cancer types, most frequently in pancreatic (>  60%), colorectal (>  40%), and lung cancers, drive oncogenic processes through overactivation of proliferation. The G12C mutation of KRAS protein is especially abundant in the case of these types of malignancies. Despite its key importance in human disease, KRAS was assumed to be non-druggable for a long time since t he protein seemingly lacks potential drug-binding ...
Source: Cancer and Metastasis Reviews - July 26, 2020 Category: Cancer & Oncology Source Type: research

Current therapy of advanced colorectal cancer according to RAS/RAF mutational status
AbstractColorectal cancer is a clinically and molecularly heterogeneous disease. Currently, extended RAS and BRAF mutation testing is obligatory in routine clinical practice before starting any treatment in the metastatic setting. Treatment decision making also includes assessment of the clinical condition of the patient, definition of the treatment goal, and consideration of the primary tumor site. Biological treatment is part of the first-line drug combination unless contraindicated. Mutational status is significantly associated with the outcome of patients and is strongly predictive for anti-EGFR-targeted therapy. The p...
Source: Cancer and Metastasis Reviews - July 9, 2020 Category: Cancer & Oncology Source Type: research

The effects of mutant Ras proteins on the cell signalome
AbstractThe genetic alterations in cancer cells are tightly linked to signaling pathway dysregulation. Ras is a key molecule that controls several tumorigenesis-related processes, and mutations in RAS genes often lead to unbiased intensification of signaling networks that fuel cancer progression. In this article, we review recent studies that describe mutant Ras-regulated signaling routes and their cross-talk. In addition to the two main Ras-driven signaling pathways, i.e., the RAF/MEK/ERK and PI3K/AKT/mTOR pathways, we have also collected emerging data showing the importance of Ras in other signaling pathways, including t...
Source: Cancer and Metastasis Reviews - July 9, 2020 Category: Cancer & Oncology Source Type: research

Role of linoleic acid-derived oxylipins in cancer
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - July 4, 2020 Category: Cancer & Oncology Source Type: research

The role of fibroblast activation protein in health and malignancy
AbstractFibroblast activation protein- α (FAP) is a type-II transmembrane serine protease expressed almost exclusively to pathological conditions including fibrosis, arthritis, and cancer. Across most cancer types, elevated FAP is associated with worse clinical outcomes. Despite the clear association between FAP and disease severity, th e biological reasons underlying these clinical observations remain unclear. Here we review basic FAP biology and FAP’s role in non-oncologic and oncologic disease. We further explore how FAP may worsen clinical outcomes via its effects on extracellular matrix remodeling, intrace...
Source: Cancer and Metastasis Reviews - June 29, 2020 Category: Cancer & Oncology Source Type: research

Long non-coding RNA: A recently accentuated molecule in chemoresistance in cancer
AbstractChemotherapy is one of the important and effective options for cancer treatment in the past decades. Although the response rate of initial chemotherapy is considerably high in certain types of cancers, such as ovarian cancer and lung cancer, the patients frequently suffer from chemoresistance and recurrence of disease. Recent genome-wide studies have shown that the large number of long non-coding RNAs (lncRNAs) are transcribed from the human genome and involved in many biological processes including carcinogenesis. They aberrantly regulate variety of cell functions, such as cell cycle, apoptosis, autophagy, and met...
Source: Cancer and Metastasis Reviews - June 27, 2020 Category: Cancer & Oncology Source Type: research

Regulation of breast cancer metastasis signaling by miRNAs
AbstractDespite the decline in death rate from breast cancer and recent advances in targeted therapies and combinations for the treatment of metastatic disease, metastatic breast cancer remains the second leading cause of cancer-associated death in U.S. women. The invasion –metastasis cascade involves a number of steps and multitudes of proteins and signaling molecules. The pathways include invasion, intravasation, circulation, extravasation, infiltration into a distant site to form a metastatic niche, and micrometastasis formation in a new environment. Each of thes e processes is regulated by changes in gene express...
Source: Cancer and Metastasis Reviews - June 23, 2020 Category: Cancer & Oncology Source Type: research

Multiple roles of HOX proteins in Metastasis: Let me count the ways
AbstractKnowledge of the role of HOX proteins in cancer has been steadily accumulating in the last 25 years. They are encoded by 39 HOX genes arranged in 4 distinct clusters, and have unique and redundant function in all types of cancers. Many HOX genes behave as oncogenic transcriptional factors regulating multiple pathways that are critical to malignant progression in a variety of tumors. Some HOX proteins have dual roles that are tumor-site specific, displaying both oncogenic and tumor suppressor function. The focus of this review is on how HOX proteins contribute to growth or suppression of metastasis. The review will ...
Source: Cancer and Metastasis Reviews - June 22, 2020 Category: Cancer & Oncology Source Type: research

Current therapy of KRAS-mutant lung cancer
AbstractKRAS mutations are the most frequent gain-of-function alterations in patients with lung adenocarcinoma (LADC) in the Western world. Although they have been identified decades ago, prior efforts to target KRAS signaling with single-agent therapeutic approaches such as farnesyl transferase inhibitors, prenylation inhibition, impairment of KRAS downstream signaling, and synthetic lethality screens have been unsuccessful. Moreover, the role of KRAS oncogene in LADC is still not fully understood, and its prognostic and predictive impact with regards to the standard of care therapy remains controversial. Of note, KRAS-re...
Source: Cancer and Metastasis Reviews - June 16, 2020 Category: Cancer & Oncology Source Type: research

K-Ras prenylation as a potential anticancer target
AbstractKRAS is one of the most commonly mutated oncogene and a negative predictive factor for a number of targeted therapies. Therefore, the development of targeting strategies against mutant KRAS is urgently needed. One potential strategy involves disruption of K-Ras membrane localization, which is necessary for its proper function. In this review, we summarize the current data about the importance of membrane-anchorage of K-Ras and provide a critical evaluation of this targeting paradigm focusing mainly on prenylation inhibition. Additionally, we performed a RAS mutation-specific analysis of prenylation-related drug sen...
Source: Cancer and Metastasis Reviews - June 10, 2020 Category: Cancer & Oncology Source Type: research

Lung cancer identification: a review on detection and classification
AbstractLung cancer is one of the most common diseases among humans and one of the major causes of growing mortality. Medical experts believe that diagnosing lung cancer in the early phase can reduce death with the illustration of lung nodule through computed tomography (CT) screening. Examining the vast amount of CT images can reduce the risk. However, the CT scan images incorporate a tremendous amount of information about nodules, and with an increasing number of images make their accurate assessment very challenging tasks for radiologists. Recently, various methods are evolved based on handcraft and learned approach to ...
Source: Cancer and Metastasis Reviews - June 9, 2020 Category: Cancer & Oncology Source Type: research

Tumor-stroma biomechanical crosstalk: a perspective on the role of caveolin-1 in tumor progression
AbstractTumor stiffening is a hallmark of malignancy that actively drives tumor progression and aggressiveness. Recent research has shed light onto several molecular underpinnings of this biomechanical process, which has a reciprocal crosstalk between tumor cells, stromal fibroblasts, and extracellular matrix remodeling at its core. This dynamic communication shapes the tumor microenvironment; significantly determines disease features including therapeutic resistance, relapse, or metastasis; and potentially holds the key for novel antitumor strategies. Caveolae and their components emerge as integrators of different aspect...
Source: Cancer and Metastasis Reviews - June 9, 2020 Category: Cancer & Oncology Source Type: research

Expression and function of epithelial cell adhesion molecule EpCAM: where are we after 40 years?
AbstractEpCAM (epithelial cell adhesion molecule) was discovered four decades ago as a tumor antigen on colorectal carcinomas. Owing to its frequent and high expression on carcinomas and their metastases, EpCAM serves as a prognostic marker, a therapeutic target, and an anchor molecule on circulating and disseminated tumor cells (CTCs/DTCs), which are considered the major source for metastatic cancer cells. Today, EpCAM is reckoned as a multi-functional transmembrane protein involved in the regulation of cell adhesion, proliferation, migration, stemness, and epithelial-to-mesenchymal transition (EMT) of carcinoma cells. To...
Source: Cancer and Metastasis Reviews - June 7, 2020 Category: Cancer & Oncology Source Type: research

Brain tumor vessels —a barrier for drug delivery
AbstractCancer treatment remains a challenge due to a high level ofintra- andintertumoral heterogeneity and the rapid development of chemoresistance. In the brain, this is further hampered by the blood-brain barrier that reduces passive diffusion of drugs to a minimum. Tumors grow invasively and form new blood vessels, also in brain tissue where remodeling of pre-existing vasculature is substantial. The cancer-associated vessels in the brain are considered leaky and thus could facilitate the transport of chemotherapeutic agents. Yet, brain tumors are extremely difficult to treat, and, in this review, we will address how di...
Source: Cancer and Metastasis Reviews - June 2, 2020 Category: Cancer & Oncology Source Type: research

Unraveling mucin domains in cancer and metastasis: when protectors become predators
AbstractA dynamic mucosal layer shields the epithelial cells lining the body cavities and is made up of high molecular weight, heavily glycosylated, multidomain proteins called mucins. Mucins, broadly grouped into transmembrane and secreted mucins, are the first responders to any mechanical or chemical insult to the epithelia and help maintain tissue homeostasis. However, their intrinsic properties to protect and repair the epithelia are exploited during oncogenic processes, where mucins are metamorphosed to aid the tumor cells in their malignant journey. Diverse domains, like the variable number tandem repeats (VNTR), sea...
Source: Cancer and Metastasis Reviews - June 2, 2020 Category: Cancer & Oncology Source Type: research

Biography —Ivan Robert Nabi
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - June 1, 2020 Category: Cancer & Oncology Source Type: research

Membrane tension buffering by caveolae: a role in cancer?
AbstractCaveolae are bulb-like invaginations made up of two essential structural proteins, caveolin-1 and cavins, which are abundantly present at the plasma membrane of vertebrate cells. Since their discovery more than 60  years ago, the function of caveolae has been mired in controversy. The last decade has seen the characterization of new caveolae components and regulators together with the discovery of additional cellular functions that have shed new light on these enigmatic structures. Early on, caveolae and/or caveolin-1 have been involved in the regulation of several parameters associated with cancer progression...
Source: Cancer and Metastasis Reviews - May 30, 2020 Category: Cancer & Oncology Source Type: research

Endothelial caveolin and its scaffolding domain in cancer
AbstractSince the initial reports implicating caveolin-1 (CAV1) in neoplasia, the scientific community has made tremendous strides towards understanding how CAV1-dependent signaling and caveolae assembly modulate solid tumor growth. Once a solid neoplastic tumor reaches a certain size, it will increasingly rely on its stroma to meet the metabolic demands of the rapidly proliferating cancer cells, a limitation typically but not exclusively addressed via the formation of new blood vessels. Landmark studies using xenograft tumor models have highlighted the importance of stromal CAV1 during neoplastic blood vessel growth from ...
Source: Cancer and Metastasis Reviews - May 29, 2020 Category: Cancer & Oncology Source Type: research

Caveolin-1 function at the plasma membrane and in intracellular compartments in cancer
AbstractCaveolin-1 (CAV1) is commonly considered to function as a cell surface protein, for instance in the genesis of caveolae. Nonetheless, it is also present in many intracellular organelles and compartments. The contributions of these intracellular pools to CAV1 function are generally less well understood, and this is also the case in the context of cancer. This review will summarize literature available on the role of CAV1 in cancer, highlighting particularly our understanding of the canonical (CAV1 in the plasma membrane) and non-canonical pathways (CAV1 in organelles and exosomes) linked to the dual role of the prot...
Source: Cancer and Metastasis Reviews - May 27, 2020 Category: Cancer & Oncology Source Type: research

Cutting the edge between cancerogenesis and organogenesis of the pancreatic endocrine lineage allocation —comprehensive review of the genes Synaptotagmin 13 and 533041C22 Rik in epithelial-to-mesenchymal transition
AbstractIn the past years, a multitude of studies has been published in the field of pancreatic organogenesis to interrogate the critical regulators of endocrine lineage segregation. Preliminary, transcription factors are guiding the transcriptional hierarchy of the endocrine specified cells, underpinning the importance of open chromatin formation. Signaling pathways either inhibit or accelerate the transcriptional landscape of pancreatic organogenesis. Thus, the fine-tuned process in the former pancreatic multipotent progenitors in the mechanism of lineage segregation needs to be elucidated more precisely for unraveling t...
Source: Cancer and Metastasis Reviews - May 24, 2020 Category: Cancer & Oncology Source Type: research

Collagen biology making inroads into prognosis and treatment of cancer progression and metastasis
AbstractProgression through dissemination to tumor-surrounding tissues and metastasis development is a hallmark of cancer that requires continuous cell-to-cell interactions and tissue remodeling. In fact, metastization can be regarded as a tissue disease orchestrated by cancer cells, leading to neoplastic colonization of new organs. Collagen is a major component of the extracellular matrix (ECM), and increasing evidence suggests that it has an important role in cancer progression and metastasis. Desmoplasia and collagen biomarkers have been associated with relapse and death in cancer patients. Despite the increasing intere...
Source: Cancer and Metastasis Reviews - May 23, 2020 Category: Cancer & Oncology Source Type: research

Tyrosine phosphorylation of tumor cell caveolin-1: impact on cancer progression
AbstractCaveolin-1 (CAV1) has long been implicated in cancer progression, and while widely accepted as an oncogenic protein, CAV1 also has tumor suppressor activity. CAV1 was first identified in an early study as the primary substrate of Src kinase, a potent oncoprotein, where its phosphorylation correlated with cellular transformation. Indeed, CAV1 phosphorylation on tyrosine-14 (Y14; pCAV1) has been associated with several cancer-associated processes such as focal adhesion dynamics, tumor cell migration and invasion, growth suppression, cancer cell metabolism, and mechanical and oxidative stress. Despite this, a clear un...
Source: Cancer and Metastasis Reviews - May 21, 2020 Category: Cancer & Oncology Source Type: research

The emerging role of Wnt5a in the promotion of a pro-inflammatory and immunosuppressive tumor microenvironment
AbstractWnt5a is the prototypical activator of the non-canonical Wnt pathways, and its overexpression has been implicated in the progression of several tumor types by promoting cell motility, invasion, EMT, and metastasis. Recent evidences have revealed a novel role of Wnt5a in the phosphorylation of the NF- κB subunit p65 and the activation of the NF-κB pathway in cancer cells. In this article, we review the molecular mechanisms and mediators defining a Wnt5a/NF-κB signaling pathway and propose that the aberrant expression of Wnt5a in some tumors drives a Wnt5a/NF-κB/IL-6/STAT3 positive feedback lo...
Source: Cancer and Metastasis Reviews - May 20, 2020 Category: Cancer & Oncology Source Type: research

Caveolin and lipid domains –close companions in managing cellular pathways
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - May 16, 2020 Category: Cancer & Oncology Source Type: research

Preface
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - May 16, 2020 Category: Cancer & Oncology Source Type: research

MDA-9/Syntenin/SDCBP: new insights into a unique multifunctional scaffold protein
AbstractTumor metastasis comprises a series of coordinated events that culminate in dissemination of cancer cells to distant sites within the body representing the greatest challenge impeding effective therapy of cancer and the leading cause of cancer-associated morbidity. Cancer cells exploit multiple genes and pathways to colonize to distant organs. These pathways are integrated and regulated at different levels by cellular- and extracellular-associated factors. Defining the genes and pathways that govern metastasis can provide new targets for therapeutic intervention. Melanoma differentiation associated gene-9 (mda-9) (...
Source: Cancer and Metastasis Reviews - May 14, 2020 Category: Cancer & Oncology Source Type: research

Molecular and cellular mechanisms underlying brain metastasis of breast cancer
AbstractMetastasis of cancer cells to the brain occurs frequently in patients with certain subtypes of breast cancer. In particular, patients with HER2-positive or triple-negative breast cancer are at high risk for the development of brain metastases. Despite recent advances in the treatment of primary breast tumors, the prognosis of breast cancer patients with brain metastases remains poor. A better understanding of the molecular and cellular mechanisms underlying brain metastasis might be expected to lead to improvements in the overall survival rate for these patients. Recent studies have revealed complex interactions be...
Source: Cancer and Metastasis Reviews - May 13, 2020 Category: Cancer & Oncology Source Type: research

Epigenetic dynamics in cancer stem cell dormancy
AbstractCancer remains one of the most challenging diseases despite significant advances of early diagnosis and therapeutic treatments. Cancerous tumors are composed of various cell types including cancer stem cells capable of self-renewal, proliferation, differentiation, and invasion of distal tumor sites. Most notably, these cells can enter a dormant cellular state that is resistant to conventional therapies. Thereby, cancer stem cells have the intrinsic potential for tumor initiation, tumor growth, metastasis, and tumor relapse after therapy. Both genetic and epigenetic alterations are attributed to the formation of mul...
Source: Cancer and Metastasis Reviews - May 12, 2020 Category: Cancer & Oncology Source Type: research

Glycosylation and raft endocytosis in cancer
AbstractChanges in glycosylation on proteins or lipids are one of the hallmarks of tumorigenesis. In many cases, it is still not understood how glycan information is translated into biological function. In this review, we discuss at the example of specific cancer-related glycoproteins how their endocytic uptake into eukaryotic cells is tuned by carbohydrate modifications. For this, we not only focus on overall uptake rates, but also illustrate how different uptake processes —dependent or not on the conventional clathrin machinery—are used under given glycosylation conditions. Furthermore, we discuss the role of...
Source: Cancer and Metastasis Reviews - May 9, 2020 Category: Cancer & Oncology Source Type: research

Solute transporters and malignancy: establishing the role of uptake transporters in breast cancer and breast cancer metastasis
AbstractThe solute carrier (SLC) superfamily encompasses a large variety of membrane-bound transporters required to transport a diverse array of substrates over biological membranes. Physiologically, they are essential for nutrient uptake, ion transport and waste removal. However, accumulating evidence suggest that up- and/or downregulation of SLCs may play a pivotal role in the pathogenesis of human malignancy. Endogenous substrates of SLCs include oestrogen and its conjugates, the handling of which may be of importance in hormone-dependent cancers. The SLCs play a significant role in the handling of therapeutic agents in...
Source: Cancer and Metastasis Reviews - May 9, 2020 Category: Cancer & Oncology Source Type: research

CDK7 inhibitors as anticancer drugs
AbstractCyclin-dependent kinase 7 (CDK7), along with cyclin H and MAT1, forms the CDK-activating complex (CAK), which directs progression through the cell cyclevia T-loop phosphorylation of cell cycle CDKs. CAK is also a component of the general transcription factor, TFIIH. CDK7-mediated phosphorylation of RNA polymerase II (Pol II) at active gene promoters permits transcription. Cell cycle dysregulation is an established hallmark of cancer, and aberrant control of transcriptional processes, through diverse mechanisms, is also common in many cancers. Furthermore, CDK7 levels are elevated in a number of cancer types and are...
Source: Cancer and Metastasis Reviews - May 8, 2020 Category: Cancer & Oncology Source Type: research

Wnts and the hallmarks of cancer
AbstractSince the discovery of the first mammalian Wnt proto-oncogene in virus-induced mouse mammary tumors almost four decades ago, Wnt signaling pathway and its involvement in cancers have been extensively investigated. Activation of this evolutionarily conserved pathway promotes cancer developmentvia diverse mechanisms. Cancer is a complex disease and one outstanding conceptual framework for understanding its biology is the “Hallmarks of Cancer”. In this review, we focus on the involvement of Wnt signaling in the ten hallmarks of human cancer. These widespread roles of Wnt signaling in human cancers highligh...
Source: Cancer and Metastasis Reviews - May 8, 2020 Category: Cancer & Oncology Source Type: research

Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19?
AbstractSevere coronavirus disease (COVID-19) is characterized by pulmonary hyper-inflammation and potentially life-threatening “cytokine storms”. Controlling the local and systemic inflammatory response in COVID-19 may be as important as anti-viral therapies. Endogenous lipid autacoid mediators, referred to as eicosanoids, play a critical role in the induction of inflammation and pro-inflammatory cytokine production. SA RS-CoV-2 may trigger a cell death (“debris”)-induced “eicosanoid storm”, including prostaglandins and leukotrienes, which in turn initiates a robust inflammatory respons...
Source: Cancer and Metastasis Reviews - May 8, 2020 Category: Cancer & Oncology Source Type: research

FOXO transcription factor family in cancer and metastasis
AbstractForkhead box O (FOXO) transcription factors regulate diverse biological processes, affecting development, metabolism, stem cell maintenance and longevity. They have also been increasingly recognised as tumour suppressors through their ability to regulate genes essential for cell proliferation, cell death, senescence, angiogenesis, cell migration and metastasis. Mechanistically, FOXO proteins serve as key connection points to allow diverse proliferative, nutrient and stress signals to converge and integrate with distinct gene networks to control cell fate, metabolism and cancer development. In consequence, deregulat...
Source: Cancer and Metastasis Reviews - May 5, 2020 Category: Cancer & Oncology Source Type: research

Clinical utility of circulating tumor DNA as a response and follow-up marker in cancer therapy
AbstractResponse evaluation for cancer treatment consists primarily of clinical and radiological assessments. In addition, a limited number of serum biomarkers that assess treatment response are available for a small subset of malignancies. Through recent technological innovations, new methods for measuring tumor burden and treatment response are becoming available. By utilization of highly sensitive techniques, tumor-specific mutations in circulating DNA can be detected and circulating tumor DNA (ctDNA) can be quantified. These so-called liquid biopsies provide both molecular information about the genomic composition of t...
Source: Cancer and Metastasis Reviews - May 4, 2020 Category: Cancer & Oncology Source Type: research

RNA-biology ruling cancer progression? Focus on 3 ′UTRs and splicing
AbstractThe protein-coding regions of mRNAs have the information to make proteins and hence have been at the center of attention for understanding altered protein functions in disease states, including cancer. Indeed, the discovery of genomic alterations and driver mutations that change protein levels and/or activity has been pivotal in our understanding of cancer biology. However, to better understand complex molecular mechanisms that are deregulated in cancers, we also need to look at non-coding parts of mRNAs, including 3 ′UTRs (untranslated regions), which control mRNA stability, localization, and translation eff...
Source: Cancer and Metastasis Reviews - May 2, 2020 Category: Cancer & Oncology Source Type: research

Caveola-forming proteins and prostate cancer
AbstractCaveolae are specialised and dynamic plasma membrane subdomains, involved in many cellular functions including endocytosis, signal transduction, mechanosensing and lipid storage, trafficking, and metabolism. Two protein families are indispensable for caveola formation and function, namely caveolins and cavins. Mutations of genes encoding these caveolar proteins cause serious pathological conditions such as cardiomyopathies, skeletal muscle diseases, and lipodystrophies. Deregulation of caveola-forming protein expression is associated with many types of cancers including prostate cancer. The distinct function of sec...
Source: Cancer and Metastasis Reviews - May 1, 2020 Category: Cancer & Oncology Source Type: research

The role of lipid species in membranes and cancer-related changes
AbstractSeveral studies have demonstrated interactions between the two leaflets in membrane bilayers and the importance of specific lipid species for such interaction and membrane function. We here discuss these investigations with a focus on the sphingolipid and cholesterol-rich lipid membrane domains called lipid rafts, including the small flask-shaped invaginations called caveolae, and the importance of such membrane structures in cell biology and cancer. We discuss the possible interactions between the very long-chain sphingolipids in the outer leaflet of the plasma membrane and the phosphatidylserine species PS 18:0/1...
Source: Cancer and Metastasis Reviews - April 20, 2020 Category: Cancer & Oncology Source Type: research

Flotillin membrane domains in cancer
AbstractFlotillins 1 and 2 are two ubiquitous, highly conserved homologous proteins that assemble to form heterotetramers at the cytoplasmic face of the plasma membrane in cholesterol- and sphingolipid-enriched domains. Flotillin heterotetramers can assemble into large oligomers to form molecular scaffolds that regulate the clustering of at the plasma membrane and activity of several receptors. Moreover, flotillins are upregulated in many invasive carcinomas and also in sarcoma, and this is associated with poor prognosis and metastasis formation. When upregulated, flotillins promote plasma membrane invagination and induce ...
Source: Cancer and Metastasis Reviews - April 15, 2020 Category: Cancer & Oncology Source Type: research

Caveolin-1, a master regulator of cellular senescence
AbstractCellular senescence is a feature of most somatic cells. It is characterized by an irreversible cell cycle arrest and by the ability to secrete a plethora of mediators of inflammation and growth factors, which can alter the senescent cell ’s microenvironment. Senescent cells accumulate in tissues over time and contribute to both aging and the development of age-associated diseases. Senescent cells have antagonistic pleiotropic roles in cancer. Given the inability of senescent cells to proliferate, cellular senescence is a powerful tumor suppressor mechanism in young individuals. However, accumulation of senesc...
Source: Cancer and Metastasis Reviews - April 11, 2020 Category: Cancer & Oncology Source Type: research

Emerging links between endosomal pH and cancer
AbstractExtracellular acidification is a well-known driver of tumorigenesis that has been extensively studied. In contrast, the role of endosomal pH is novel and relatively unexplored. There is emerging evidence from a growing number of studies showing that the pH of endosomal compartments controls proliferation, migration, stemness, and sensitivity to chemoradiation therapy in a variety of tumors. Endosomes are a crucial hub, mediating cellular communication with the external environment. By finely regulating the sorting and trafficking of vesicular cargo for degradation or recycling, endosomal pH determines the fate of p...
Source: Cancer and Metastasis Reviews - April 6, 2020 Category: Cancer & Oncology Source Type: research

BRMS1: a multifunctional signaling molecule  in metastasis
AbstractDespite high mortality rates, molecular understanding of metastasis remains limited. It can be regulated by both pro- and anti-metastasis genes. The metastasis suppressor, breast cancer metastasis suppressor 1 (BRMS1), has been positively correlated with patient outcomes, but molecular functions are still being characterized. BRMS1 has been implicated in focal adhesion kinase (FAK), epidermal growth factor receptor (EGFR), and NF- κB signaling pathways. We review evidence that BRMS1 regulates these vast signaling pathways through chromatin remodeling as a member of mSin3 histone deacetylase complexes. (Source...
Source: Cancer and Metastasis Reviews - March 30, 2020 Category: Cancer & Oncology Source Type: research

Professor Samuel C. Brooks, Jr., Ph.D. (1928 –2019)
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - March 16, 2020 Category: Cancer & Oncology Source Type: research

KISS1 in metastatic cancer research and treatment: potential and paradoxes
AbstractThe significance of KISS1 goes beyond its original discovery as a metastasis suppressor. Its function as a neuropeptide involved in diverse physiologic processes is more well studied. Enthusiasm regarding KISS1 has cumulated in  clinical trials in multiple fields related to reproduction and metabolism. But its cancer therapeutic space is unsettled. This review focuses on collating data from cancer and non-cancer fields in order to understand shared and disparate signaling that might inform clinical development in the canc er therapeutic and biomarker space. Research has focused on amino acid residues 68-121 (k...
Source: Cancer and Metastasis Reviews - March 9, 2020 Category: Cancer & Oncology Source Type: research

How progressive cancer endangers the heart: an intriguing and underestimated problem
AbstractSince it came into being as a discipline, cardio-oncology has focused on the prevention and treatment of cardiotoxicity induced by antitumor chemotherapy and radiotherapy. Over time, it has been proved that even more detrimental is the direct effect generated by cancer cells that release pro-cachectic factors in the bloodstream. Secreted molecules target different organs at a distance, including the heart. Inflammatory and neuronal modulators released by the tumor bulk, either as free molecules or through exosomes, contribute to the pathogenesis of cardiac disease. Progressive cancer causes cachexia and severe card...
Source: Cancer and Metastasis Reviews - March 9, 2020 Category: Cancer & Oncology Source Type: research

Pediatric medulloblastoma in the molecular era: what are the surgical implications?
AbstractPediatric brain tumors are the leading cause of childhood cancer mortality with medulloblastoma (MB) representing the most frequent malignant tumor. Although standardization of therapy resulted in a 2-fold reduction in mortality in patients with MB by 2002, it became clear that further improvements in clinical outcome would require a deeper understanding of the biology of MB. Employing the four main molecular MB subgroups (Wnt, Shh, Group 3 and Group 4), a restratification into clinicogenomic risk categories quantified an unacceptable survival for the high-risk group, urging researchers to focus their efforts towar...
Source: Cancer and Metastasis Reviews - February 24, 2020 Category: Cancer & Oncology Source Type: research

New insights into antimetastatic signaling pathways of melatonin in skeletomuscular sarcoma of childhood and adolescence
AbstractMelatonin is an indole produced by the pineal gland at night under normal light or dark conditions, and its levels, which are higher in children than in adults, begin to decrease prior to the onset of puberty and continue to decline thereafter. Apart from circadian regulatory actions, melatonin has significant apoptotic, angiogenic, oncostatic, and antiproliferative effects on various cancer cells. Particularly, the ability of melatonin to inhibit skeletomuscular sarcoma, which most commonly affects children, teenagers, and young adults, is substantial. In the past few decades, the vast majority of references have ...
Source: Cancer and Metastasis Reviews - February 21, 2020 Category: Cancer & Oncology Source Type: research

Correction to: Neurological complications of pediatric cancer
The authors have noticed a typographical error in the published article. (Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - February 12, 2020 Category: Cancer & Oncology Source Type: research