A “New Radiation”—shining light on cancer
AbstractThere is renewed interest in novel spectroscopic techniques for molecular interrogation. Inelastic light scattering techniques can provide real-time  phenotypic identification of tissue and cellular state. Here we review Raman spectroscopy as a powerful technique for the identification of cancerous tissue and tumor boundaries. (Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - November 13, 2020 Category: Cancer & Oncology Source Type: research

Cyclin-dependent kinase inhibitors in head and neck cancer and glioblastoma —backbone or add-on in immune-oncology?
AbstractCyclin-dependent kinases (CDK) control the cell cycle and play a crucial role in oncogenesis. Pharmacologic inhibition of CDK has contributed to the recent clinical approval of dual CDK4/6 inhibitors for the treatment of breast and small cell lung cancer. While the anticancer cell effects of CDK inhibitors are well-established, preclinical and early clinical studies describe additional mechanisms of action such as chemo- and radiosensitization or immune stimulation. The latter offers great potential to incorporate CDK inhibitors in immune-based treatments. However, dosing schedules and accurate timing of each combi...
Source: Cancer and Metastasis Reviews - November 8, 2020 Category: Cancer & Oncology Source Type: research

Metastasis is a highly stressful process
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - November 6, 2020 Category: Cancer & Oncology Source Type: research

Visualizing cancer extravasation: from mechanistic studies to drug development
AbstractMetastasis is a multistep process that accounts for the majority of cancer-related death. By the end of metastasize dissemination, circulating tumor cells (CTC) need to extravasate the blood vessels at metastatic sites to form new colonization. Although cancer cell extravasation is a crucial step in cancer metastasis, it has not been successfully targeted by current anti-metastasis strategies due to the lack of a thorough understanding of the molecular mechanisms that regulate this process. This review focuses on recent progress in cancer extravasation visualization techniques, including the development of bothin v...
Source: Cancer and Metastasis Reviews - November 6, 2020 Category: Cancer & Oncology Source Type: research

Secreted frizzled-related protein 2: a key player in noncanonical Wnt signaling and tumor angiogenesis
AbstractSecreted frizzled-related proteins (SFRP) are glycoproteins containing a so-called frizzled-like cysteine-rich domain. This domain enables them to bind to Wnt ligands or frizzled (FzD) receptors, making potent regulators of Wnt signaling. As Wnt signaling is often altered in cancer, it is not surprising that Wnt regulators such as SFRP proteins are often differentially expressed in the tumor microenvironment, both in a metastatic and non-metastatic setting. Indeed, SFRP2 is shown to be specifically upregulated in the tumor vasculature of several types of cancer. Several studies investigated the functional role of S...
Source: Cancer and Metastasis Reviews - November 2, 2020 Category: Cancer & Oncology Source Type: research

Beyond tradition and convention: benefits of non-traditional model organisms in cancer research
AbstractTraditional laboratory model organisms are indispensable for cancer research and have provided insight into numerous mechanisms that contribute to cancer development and progression in humans. However, these models do have some limitations, most notably related to successful drug translation, because traditional model organisms are often short-lived, small-bodied, genetically homogeneous, often immunocompromised, are not exposed to natural environments shared with humans, and usually do not develop cancer spontaneously. We propose that assimilating information from a variety of long-lived, large, genetically divers...
Source: Cancer and Metastasis Reviews - October 28, 2020 Category: Cancer & Oncology Source Type: research

Centrosome amplification: a quantifiable cancer cell trait with prognostic value in solid malignancies
AbstractNumerical and/or structural centrosome amplification (CA) is a hallmark of cancers that is often associated with the aberrant tumor karyotypes and poor clinical outcomes. Mechanistically, CA compromises mitotic fidelity and leads to chromosome instability (CIN), which underlies tumor initiation and progression. Recent technological advances in microscopy and image analysis platforms have enabled better-than-ever detection and quantification of centrosomal aberrancies in cancer. Numerous studies have thenceforth correlated the presence and the degree of CA with indicators of poor prognosis such as higher tumor grade...
Source: Cancer and Metastasis Reviews - October 26, 2020 Category: Cancer & Oncology Source Type: research

The role of caspase-8 in the tumor microenvironment of ovarian cancer
AbstractCaspase-8 is an aspartate-specific cysteine protease, which is best known for its apoptotic functions. Caspase-8 is placed at central nodes of multiple signal pathways, regulating not only the cell cycle but also the invasive and metastatic cell behavior, the immune cell homeostasis and cytokine production, which are the two major components of the tumor microenvironment (TME). Ovarian cancer often has dysregulated caspase-8 expression, leading to imbalance between its apoptotic and non-apoptotic functions within the tumor and the surrounding milieu. The downregulation of caspase-8 in ovarian cancer seems to be lin...
Source: Cancer and Metastasis Reviews - October 6, 2020 Category: Cancer & Oncology Source Type: research

Interaction between adipose tissue and cancer cells: role for cancer progression
AbstractEnvironment surrounding tumours are now recognized to play an important role in tumour development and progression. Among the cells found in the tumour environment, adipocytes from adipose tissue establish a vicious cycle with cancer cells to promote cancer survival, proliferation, metastasis and treatment resistance. This cycle is particularly of interest in the context of obesity, which has been found as a cancer risk factor. Cancers cells can reprogram adipocyte physiology leading to an “activated” phenotype characterized by delipidation and secretion of inflammatory adipokines. The adipocyte secreti...
Source: Cancer and Metastasis Reviews - October 1, 2020 Category: Cancer & Oncology Source Type: research

Novel regulation of Ras proteins by direct tyrosine phosphorylation and dephosphorylation
AbstractSomatic mutations in theRAS genes are frequent in human tumors, especially in pancreatic, colorectal, and non-small-cell lung cancers. Such mutations generally decrease the ability of Ras to hydrolyze GTP, maintaining the protein in a constitutively active GTP-bound form that drives uncontrolled cell proliferation. Efforts to develop drugs that target Ras oncoproteins have been unsuccessful. Recent emerging data suggest that Ras regulation is more complex than the scientific community has believed for decades. In this review, we summarize advances in the “textbook” view of Ras activation. We also discus...
Source: Cancer and Metastasis Reviews - September 15, 2020 Category: Cancer & Oncology Source Type: research

Guest editorial/preface
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - September 15, 2020 Category: Cancer & Oncology Source Type: research

Current methods in translational cancer research
AbstractRecent developments in pre-clinical screening tools, that more reliably predict the clinical effects and adverse events of candidate therapeutic agents, has ushered in a new era of drug development and screening. However, given the rapid pace with which these models have emerged, the individual merits of these translational research tools warrant careful evaluation in order to furnish clinical researchers with appropriate information to conduct pre-clinical screening in an accelerated and rational manner. This review assesses the predictive utility of both well-established and emerging pre-clinical methods in terms...
Source: Cancer and Metastasis Reviews - September 13, 2020 Category: Cancer & Oncology Source Type: research

Galectin-3: an immune checkpoint target for musculoskeletal tumor patients
AbstractIn the past decade, the development of immune checkpoint inhibitors in oncological clinical settings was in the forefront. However, the interest in musculoskeletal tumor patients as candidates for checkpoint inhibition remains underserved. Here, we are forwarding evidence proposing that galectin-3 (Gal-3) is an additional immune factor in the checkpoint processes. This review is the result of a large-scale cohort study depicting that overexpression of Gal-3 was widely prevalent in patients with musculoskeletal tumors, whereas T cell infiltrations were generally suppressed in the tumor microenvironment. Targeting Ga...
Source: Cancer and Metastasis Reviews - September 13, 2020 Category: Cancer & Oncology Source Type: research

Gastric cancer: a comprehensive review of current and future treatment strategies
AbstractGastric cancer remains a major unmet clinical problem with over 1 million new cases worldwide. It is the fourth most commonly occurring cancer in men and the seventh most commonly occurring cancer in women. A major fraction of gastric cancer has been linked to variety of pathogenic infections including but not limited to Helicobacter pylori (H. pylori) or Epstein Barr virus (EBV). Strategies are being pursued to prevent gastric cancer development such asH. pylori eradication, which has helped to prevent significant proportion of gastric cancer. Today, treatments have helped to manage this disease and the 5-year sur...
Source: Cancer and Metastasis Reviews - September 6, 2020 Category: Cancer & Oncology Source Type: research

Biographies
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - August 31, 2020 Category: Cancer & Oncology Source Type: research

Platelets in aging and cancer —“double-edged sword”
AbstractPlatelets control hemostasis and play a key role in inflammation and immunity. However, platelet function may change during aging, and a role for these versatile cells in many age-related pathological processes is emerging. In addition to a well-known role in cardiovascular disease, platelet activity is now thought to contribute to cancer cell metastasis and tumor-associated venous thromboembolism (VTE) development. Worldwide, the great majority of all patients with cardiovascular disease and some with cancer receive anti-platelet therapy to reduce the risk of thrombosis. However, not only do thrombotic diseases re...
Source: Cancer and Metastasis Reviews - August 31, 2020 Category: Cancer & Oncology Source Type: research

Preface
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - August 23, 2020 Category: Cancer & Oncology Source Type: research

Coordinated dysregulation of cancer progression by the HER family and p21-activated kinases
AbstractMost epithelial cancer types are polygenic in nature and are driven by coordinated dysregulation of multiple regulatory pathways, genes, and protein modifications. The process of coordinated regulation of cancer promoting pathways in response to extrinsic and intrinsic signals facilitates the dysregulation of several pathways with complementary functions, contributing to the hallmarks of cancer. Dysregulation and hyperactivation of cell surface human epidermal growth factor receptors (HERs) and cytoskeleton remodeling by p21-activated kinases (PAKs) are two prominent interconnected aspects of oncogenesis. We briefl...
Source: Cancer and Metastasis Reviews - August 20, 2020 Category: Cancer & Oncology Source Type: research

Dynamically encoded reactivity of Ras enzymes: opening new frontiers for drug discovery
AbstractDecoding molecular flexibility in order to understand and predict biological processes —applying the principles of dynamic-structure-activity relationships (DSAR)—becomes a necessity when attempting to design selective and specific inhibitors of a protein that has overlapping interaction surfaces with its upstream and downstream partners along its signaling cascade. Ras proteins a re molecular switches that meet this definition perfectly. The close-lying P-loop and the highly flexible switch I and switch II regions are the site of nucleotide-, assisting-, and effector-protein binding. Oncogenic mutation...
Source: Cancer and Metastasis Reviews - August 19, 2020 Category: Cancer & Oncology Source Type: research

Molecular mediators of peritoneal metastasis in pancreatic cancer
AbstractPancreatic cancer is the third leading cause of cancer death in the USA, and pancreatic ductal adenocarcinoma (PDA) constitutes 85% of pancreatic cancer diagnoses. PDA frequently metastasizes to the peritoneum, but effective treatment of peritoneal metastasis remains a clinical challenge. Despite this unmet need, understanding of the biological mechanisms that contribute to development and progression of PDA peritoneal metastasis is sparse. By contrast, a vast number of studies have investigated mechanisms of peritoneal metastasis in ovarian and gastric cancers. Here, we contrast similarities and differences betwee...
Source: Cancer and Metastasis Reviews - August 10, 2020 Category: Cancer & Oncology Source Type: research

A systems biology approach to discovering pathway signaling dysregulation in metastasis
AbstractTotal metastatic burden is the primary cause of death for many cancer patients. While the process of metastasis has been studied widely, much remains to be understood. Moreover, few agents have been developed that specifically target the major steps of the metastatic cascade. Many individual genes and pathways have been implicated in metastasis but a holistic view of how these interact and cooperate to regulate and execute the process remains somewhat rudimentary. It is unclear whether all of the signaling features that regulate and execute metastasis are yet fully understood. Novel features of a complex system suc...
Source: Cancer and Metastasis Reviews - August 9, 2020 Category: Cancer & Oncology Source Type: research

Rho GTPases in cancer radiotherapy and metastasis
AbstractDespite treatment advances, radioresistance and metastasis markedly impair the benefits of radiotherapy to patients with malignancies. Functioning as molecular switches, Rho guanosine triphosphatases (GTPases) have well-recognized roles in regulating various downstream signaling pathways in a wide range of cancers. In recent years, accumulating evidence indicates the involvement of Rho GTPases in cancer radiotherapeutic efficacy and metastasis, as well as radiation-induced metastasis. The functions of Rho GTPases in radiotherapeutic efficacy are divergent and context-dependent; thereby, a comprehensive integration ...
Source: Cancer and Metastasis Reviews - August 7, 2020 Category: Cancer & Oncology Source Type: research

Splice variants of RAS —translational significance
AbstractOne of the mechanisms potentially explaining the discrepancy between the number of human genes and the functional complexity of organisms is generating alternative splice variants, an attribute of the vast majority of multi-exon genes. Members of the RAS family, such as NRAS, KRAS and HRAS, all of which are of significant importance in cancer biology, are no exception. The structural and functional differences of these splice variants, particularly if they contain the canonical (and therefore routinely targeted for diagnostic purposes)hot spot mutations, pose a significant challenge for targeted therapies. We must ...
Source: Cancer and Metastasis Reviews - August 7, 2020 Category: Cancer & Oncology Source Type: research

Small molecule inhibitors of RAS proteins with oncogenic mutations
AbstractRAS proteins control a number of essential cellular processes as molecular switches in the human body. Presumably due to their important signalling role, RAS proteins are among the most frequently mutated oncogenes in human cancers. Hence, numerous efforts were done to develop appropriate therapies for RAS-mutant cancers in the last three decades. This review aimed to collect all of the reported small molecules that affect RAS signalling. These molecules can be divided in four main branches. First, we address approaches blocking RAS membrane association. Second, we focus on the stabilization efforts of non-producti...
Source: Cancer and Metastasis Reviews - August 6, 2020 Category: Cancer & Oncology Source Type: research

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 28, 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 28, 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 25, 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 8, 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 8, 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 3, 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 28, 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 26, 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 22, 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 21, 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 15, 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 9, 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 8, 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 8, 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 6, 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 1, 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 1, 2020 Category: Cancer & Oncology Source Type: research

Biography —Ivan Robert Nabi
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - May 31, 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 29, 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 28, 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 26, 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 23, 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 22, 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 20, 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 19, 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 15, 2020 Category: Cancer & Oncology Source Type: research