Functional disparities within the TIMP family in cancer: hints from molecular divergence
AbstractThe members of the tissue inhibitor of metalloproteinase (TIMP) family (TIMP-1, 2, 3, 4) are prominently appreciated as natural inhibitors of cancer-promoting metalloproteinases. However, clinical and recent functional studies indicate that some of them correlate with bad prognosis and contribute to the progression of cancer and metastasis, pointing towards mechanisms beyond inhibition of cancer-promoting proteases. Indeed, it is increasingly recognized that TIMPs are multi-functional proteins mediating a variety of cellular effects including direct cell signaling. Our aim was to provide comprehensive information t...
Source: Cancer and Metastasis Reviews - September 16, 2019 Category: Cancer & Oncology Source Type: research

Cell surface –anchored serine proteases in cancer progression and metastasis
AbstractOver the last two decades, a novel subgroup of serine proteases, the cell surface –anchored serine proteases, has emerged as an important component of the human degradome, and several members have garnered significant attention for their roles in cancer progression and metastasis. A large body of literature describes that cell surface–anchored serine proteases are deregulated in cancer and that they contribute to both tumor formation and metastasis through diverse molecular mechanisms. The loss of precise regulation of cell surface–anchored serine protease expression and/or catalytic activity may ...
Source: Cancer and Metastasis Reviews - September 16, 2019 Category: Cancer & Oncology Source Type: research

Update on gastric cancer treatments and gene therapies
AbstractGastric cancer is an active topic of clinical and basic research due to high morbidity and mortality. To date, gastrectomy and chemotherapy are the only therapeutic options for gastric cancer patients, but drug resistance, either acquired or primary, is the main cause for treatment failure. Differences in development and response to cancer treatments have been observed among ethnically diverse GC patient populations. In spite of major incidence, GC Asian patients have a significantly better prognosis and response to treatments than Caucasian ones due to genetic discordances between the two populations. Gene therapy...
Source: Cancer and Metastasis Reviews - September 5, 2019 Category: Cancer & Oncology Source Type: research

The role of proteases in epithelial-to-mesenchymal cell transitions in cancer
AbstractChanging the characteristics of cells from epithelial states to mesenchymal properties is a key process involved in developmental and physiological processes as well as in many diseases with cancer as the most prominent example. Nowadays, a great deal of work and literature concerns the understanding of the process of epithelial-to-mesenchymal transition (EMT) in terms of its molecular regulation and its implications for cancer. Similar statements can certainly be made regarding the investigation of the more than 500 proteases typically encoded by a mammalian genome. Specifically, the impact of proteases on tumor b...
Source: Cancer and Metastasis Reviews - September 3, 2019 Category: Cancer & Oncology Source Type: research

Role of meprin metalloproteases in metastasis and tumor microenvironment
AbstractA crucial step for tumor cell extravasation and metastasis is the migration through the extracellular matrix, which requires proteolytic activity. Hence, proteases, particularly matrix metalloproteases (MMPs), have been discussed as therapeutic targets and their inhibition should diminish tumor growth and metastasis. The metalloproteases meprin α and meprin β are highly abundant on intestinal enterocytes and their expression was associated with different stages of colorectal cancer. Due to their ability to cleave extracellular matrix (ECM) components, they were suggested as pro-tumorigenic enzymes. Addit...
Source: Cancer and Metastasis Reviews - September 3, 2019 Category: Cancer & Oncology Source Type: research

Proteolytic chemokine cleavage as a regulator of lymphocytic infiltration in solid tumors
AbstractIn the past decade, immune-based therapies such as monoclonal antibodies against tumor epitopes or immune checkpoint inhibitors have become an integral part of contemporary cancer treatment in many entities. However, a fundamental prerequisite for the success of such therapies is a sufficient trafficking of tumor-infiltrating lymphocytes into the tumor microenvironment. This infiltration is facilitated by chemokines, a group of about 50 small proteins capable of chemotactically guiding leukocytes. Proteolytic inactivation of chemokines leading to an impaired infiltration of immune effector cells appears to be an ef...
Source: Cancer and Metastasis Reviews - September 3, 2019 Category: Cancer & Oncology Source Type: research

Specifically targeting cancer proliferation and metastasis processes: the development of matriptase inhibitors
AbstractMatriptase is a type II transmembrane serine protease, which has been suggested to play critical roles in numerous pathways of biological developments. Matriptase is the activator of several oncogenic proteins, including urokinase-type plasminogen activator (uPA), hepatocyte growth factor (HGF) and protease-activated receptor 2 (PAR-2). The activations of these matriptase substrates subsequently lead to the generation of plasmin, matrix metalloproteases (MMPs), and the triggers for many other signaling pathways related to cancer proliferation and metastasis. Accordingly, matriptase is considered an emerging target ...
Source: Cancer and Metastasis Reviews - August 30, 2019 Category: Cancer & Oncology Source Type: research

Correction to: Tumor pH and metastasis: a malignant process beyond hypoxia
The authors have noticed a typographical error in the published article. The term “epithelial-to-mesenchymal transition” should have been used instead of the term “endothelial-to-mesenchymal transition” throughout the manuscript. (Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - June 27, 2019 Category: Cancer & Oncology Source Type: research

It is not just the drugs that matter: the nocebo effect
AbstractThe role of psychological mechanisms in the treatment process cannot be underestimated, the well-known placebo effect unquestionably being a factor in treatment. However, there is also a dark side to the impact of mental processes on health/illness as exemplified by the nocebo effect. This phenomenon includes the emergence or exacerbation of negative symptoms associated with the therapy, but arising as a result of the patient ’s expectations, rather than being an actual complication of treatment. The exact biological mechanisms of this process are not known, but cholecystokinergic and dopaminergic systems, ch...
Source: Cancer and Metastasis Reviews - June 16, 2019 Category: Cancer & Oncology Source Type: research

Biography —Robert J. Gillies
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - June 1, 2019 Category: Cancer & Oncology Source Type: research

The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond
AbstractCancer development is a complex process that follows an intricate scenario with a dynamic interplay of selective and adaptive steps and an extensive cast of molecules and signaling pathways. Solid tumor initially grows as an avascular bulk of cells carrying oncogenic mutations until diffusion distances from the nearest functional blood vessels limit delivery of nutrients and oxygen on the one hand and removal of metabolic waste on the other one. These restrictions result in regional hypoxia and acidosis that select for adaptable tumor cells able to promote aberrant angiogenesis, remodel metabolism, acquire invasive...
Source: Cancer and Metastasis Reviews - May 10, 2019 Category: Cancer & Oncology Source Type: research

Acidosis and proteolysis in the tumor microenvironment
We describe similar changes that have been observed in cancer cells in response to an acidic microenvironment and that are associated with proteolysis and invasive and metastatic phenotypes. This includes consideration of changes observed in the intracellular trafficking of vesicles, i.e., lysosomes and exosomes, and in specialized regions of the membrane, i.e., invadopodia and caveolae. Cancer-associated cells are known to affect what is generally referred to as tumor proteolysis but little direct evidence for this being regulated by acidosis; we describe potential links that should be verified. (Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - May 8, 2019 Category: Cancer & Oncology Source Type: research

Preface
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - May 8, 2019 Category: Cancer & Oncology Source Type: research

Fugitives on the run: circulating tumor cells (CTCs) in metastatic diseases
AbstractThe presence of circulating tumor cells (CTCs) in the bloodstream signals the existence of a tumor and denotes risk of metastatic spread. CTCs can be isolated and analyzed to monitor cancer progression and therapeutic response. However, CTC isolation devices have shown considerable variation in detection rates, limiting their use as a routine diagnostic and monitoring tool. In this review, we discuss recent advances in CTC detection methodologies and associated clinical studies. We provide perspective on the future direction of CTC isolation and molecular characterization towards developing reliable biomarkers that...
Source: Cancer and Metastasis Reviews - May 3, 2019 Category: Cancer & Oncology Source Type: research

Exosomes, metastases, and the miracle of cancer stem cell markers
AbstractCancer-initiating cells (CIC) are the driving force in tumor progression. There is strong evidence that CIC fulfill this taskvia exosomes (TEX), which modulate and reprogram stroma, nontransformed cells, and non-CIC. Characterization of CIC, besides others, builds on expression of CIC markers, many of which are known as metastasis-associated molecules. We here discuss that the linkage between CIC/CIC-TEX and metastasis-associated molecules is not fortuitously, but relies on the contribution of these markers to TEX biogenesis including loading and TEX target interactions. In addition, CIC markers contribute to TEX b...
Source: Cancer and Metastasis Reviews - April 27, 2019 Category: Cancer & Oncology Source Type: research

The Warburg metabolism fuels tumor metastasis
AbstractThe Warburg effect is prevalent in human cancer. Accordingly, most cancer cells display highly elevated glycolysis without proportionally increasing pyruvate oxidation. The metastatic process imposes strong selective pressure on cancer cells, and metastasizing cancer cells experience heightened oxidative stress. By constraining mitochondrial oxidative metabolism, the Warburg effect helps cancer cells to minimize oxidative stress, thereby facilitating metastatic dissemination. The PGC1 α transcriptional coactivator is a central coordinator of oxidative metabolism. While promoting oxidative metabolism and rever...
Source: Cancer and Metastasis Reviews - April 17, 2019 Category: Cancer & Oncology Source Type: research

Intracellular pH dynamics and charge-changing somatic mutations in cancer
AbstractAn unresolved question critical for understanding cancer is how recurring somatic mutations are retained and how selective pressures drive retention. Increased intracellular pH (pHi) is common to most cancers and is an early event in cancer development. Recent work shows that recurrent somatic mutations can confer an adaptive gain in pH sensing to mutant proteins, enhancing tumorigenic phenotypes specifically at the increased pHi of cancer. Newly identified amino acid mutation signatures in cancer suggest charge-changing mutations define and shape the mutational landscape of cancer. Taken together, these results su...
Source: Cancer and Metastasis Reviews - April 13, 2019 Category: Cancer & Oncology Source Type: research

Causes, consequences, and therapy of tumors acidosis
AbstractWhile cancer is commonly described as “a disease of the genes,” it is also associated with massive metabolic reprogramming that is now accepted as a disease “Hallmark.” This programming is complex and often involves metabolic cooperativity between cancer cells and their surrounding stroma. Indeed, there is emerging clinical evid ence that interrupting a cancer’s metabolic program can improve patients’ outcomes. The most commonly observed and well-studied metabolic adaptation in cancers is the fermentation of glucose to lactic acid, even in the presence of oxygen, also known as &l...
Source: Cancer and Metastasis Reviews - March 26, 2019 Category: Cancer & Oncology Source Type: research

Molecular and functional imaging insights into the role of hypoxia in cancer aggression
AbstractHypoxia in cancers has evoked significant interest since 1955 when Thomlinson and Gray postulated the presence of hypoxia in human lung cancers, based on the observation of necrosis occurring at the diffusion limit of oxygen from the nearest blood vessel, and identified the implication of these observations for radiation therapy. Coupled with discoveries in 1953 by Gray and others that anoxic cells were resistant to radiation damage, these observations have led to an entire field of research focused on exploiting oxygenation and hypoxia to improve the outcome of radiation therapy. Almost 65  years later, tumor...
Source: Cancer and Metastasis Reviews - March 6, 2019 Category: Cancer & Oncology Source Type: research

Cause and effect of microenvironmental acidosis on bone metastases
AbstractSkeletal involvement is a frequent and troublesome complication in advanced cancers. In the process of tumor cells homing to the skeleton to form bone metastases (BM), different mechanisms allow tumor cells to interact with cells of the bone microenvironment and seed in the bone tissue. Among these, tumor acidosis has been directly associated with tumor invasion and aggressiveness in several types of cancer although it has been less explored in the context of BM. In bone, the association of local acidosis and cancer invasiveness is even more important for tumor expansion since the extracellular matrix is formed by ...
Source: Cancer and Metastasis Reviews - March 2, 2019 Category: Cancer & Oncology Source Type: research

Pro- and antitumor effects of mitochondrial reactive oxygen species
AbstractIn cancer, mitochondrial functions are commonly altered. Directly involved in metabolic reprogramming, mitochondrial plasticity confers to cancer cells a high degree of adaptability to a wide range of stresses and to the harsh tumor microenvironment. Lack of nutrients or oxygen caused by altered perfusion, metabolic needs of proliferating cells, co-option of the microenvironment, control of the immune system, cell migration and metastasis, and evasion of exogenous stress (e.g., chemotherapy) are all, at least in part, influenced by mitochondria. Mitochondria are undoubtedly one of the key contributors to cancer dev...
Source: Cancer and Metastasis Reviews - March 1, 2019 Category: Cancer & Oncology Source Type: research

Acidosis and cancer: from mechanism to neutralization
AbstractThe extracellular pH of solid tumors is unequivocally acidic due to a combination of high rates of lactic acid production (a consequence of fermentative glycolytic metabolism) and poor perfusion. This has been documented by us and others in a wide variety of solid tumor models, primarily using magnetic resonance spectroscopic imaging (MRSI). This acidity contributes to tumor progression by inducing genome instability, promoting local invasion and metastases, inhibiting anti-tumor immunity, and conferring resistance to chemo- and radio-therapies. Systemic buffer therapies can neutralize tumor acidity and has been sh...
Source: Cancer and Metastasis Reviews - February 26, 2019 Category: Cancer & Oncology Source Type: research

Pro-metastatic functions of lipoproteins and extracellular vesicles in the acidic tumor microenvironment
AbstractAlthough the overall mortality in cancer is steadily decreasing, major groups of patients still respond poorly to available treatments. The key clinical challenge discussed here relates to the inherent capacity of cancer cells to metabolically adapt to hypoxic and acidic stress, resulting in treatment resistance and a pro-metastatic behavior. Hence, a detailed understanding of stress adaptive responses is critical for the design of more rational therapeutic strategies for cancer. We will focus on the emerging role of extracellular vesicles (EVs) and lipoprotein particles in cancer cell metabolic stress adaptation a...
Source: Cancer and Metastasis Reviews - February 15, 2019 Category: Cancer & Oncology Source Type: research

Imaging tumor acidosis: a survey of the available techniques for mapping in vivo tumor pH
AbstractCancer cells are characterized by a metabolic shift in cellular energy production, orchestrated by the transcription factor HIF-1 α, from mitochondrial oxidative phosphorylation to increased glycolysis, regardless of oxygen availability (Warburg effect). The constitutive upregulation of glycolysis leads to an overproduction of acidic metabolic products, resulting in enhanced acidification of the extracellular pH (pHe ~ 6.5) , which is a salient feature of the tumor microenvironment. Despite the importance of pH and tumor acidosis, there is currently no established clinical tool available to image the s...
Source: Cancer and Metastasis Reviews - February 14, 2019 Category: Cancer & Oncology Source Type: research

Acidosis promotes tumorigenesis by activating AKT/NF- κB signaling
AbstractThe microenvironment of solid tumors is often acidic due to poor vascular perfusion, regional hypoxia, and increased glycolytic activity of tumor cells. Although acidosis is harmful to most types of cells, tumor cells seem well adapted to such harsh conditions. Moreover, overwhelming evidence indicates that tumor cells are more invasive and more aggressive in acidic conditions by a cascade of cell signaling and upregulation of oncogenic gene expression. Therefore, how extracellular acidic signals are transduced to the cytoplasm and then into the nucleus is an interesting topic to many cancer researchers. In this re...
Source: Cancer and Metastasis Reviews - February 7, 2019 Category: Cancer & Oncology Source Type: research

Na + ,HCO 3 − cotransporter NBCn1 accelerates breast carcinogenesis
AbstractCell metabolism increases during carcinogenesis. Yet, intracellular pH in solid cancer tissue is typically maintained equal to or above that of normal tissue. This is achieved through accelerated cellular acid extrusion that compensates for the enhanced metabolic acid production. Upregulated Na+,HCO3− cotransport is the predominant mechanism of net acid extrusion in human and murine breast cancer tissue, and in congruence, the protein expression of the electroneutral Na+,HCO3− cotransporter NBCn1 is increased in primary breast carcinomas and lymph node metastases compared to matched normal breast tissue...
Source: Cancer and Metastasis Reviews - February 4, 2019 Category: Cancer & Oncology Source Type: research

Extracellular acidity and increased exosome release as key phenotypes of malignant tumors
AbstractThe tumor milieu is characteristically acidic as a consequence of the fermentative metabolism of glucose that results in massive accumulation of lactic acid within the cytoplasm. Tumor cells get rid of excessive protons through exchangers that are responsible for the extracellular acidification that selects cellular clones that are more apt at surviving in this challenging and culling environment. Extracellular vesicles (EVs) are vesicles with diameters ranging from nm to μm that are released from the cells to deliver nucleic acids, proteins, and lipids to adjacent or distant cells. EVs are involved in a plethor...
Source: Cancer and Metastasis Reviews - February 4, 2019 Category: Cancer & Oncology Source Type: research

What is pH regulation, and why do cancer cells need it?
AbstractMetabolism is a continuous source of acids. To keep up with  a desired metabolic rate, tumors must establish an adequate means of clearing their acidic end-products. This homeostatic priority is achieved by various buffers, enzymes, and transporters connected through the common denominator of H+ ions. Whilst this complexity is proportionate to the importance of adequate pH control, it is problematic for developing an intuition for tracking the route taken by acids, assessing the relative importance of various acid-handling proteins, and predicting the outcomes of pharmacological inhibition or genetic alteratio...
Source: Cancer and Metastasis Reviews - February 1, 2019 Category: Cancer & Oncology Source Type: research

Biography —Stephanie Tucker
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - January 25, 2019 Category: Cancer & Oncology Source Type: research

Mucin glycoproteins block apoptosis; promote invasion, proliferation, and migration; and cause chemoresistance through diverse pathways in epithelial cancers
AbstractOverexpression of mucin glycoproteins has been demonstrated in many epithelial-derived cancers. The significance of this overexpression remains uncertain. The aim of this paper was to define the association of mucin glycoproteins with apoptosis, cell growth, invasion, migration, adhesion, and clonogenicityin vitro as well as tumor growth, tumorigenicity, and metastasisin vivo in epithelial-derived cancers by performing a systematic review of all published data. A systematic review of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was performed to identify all papers that evaluated the associ...
Source: Cancer and Metastasis Reviews - January 24, 2019 Category: Cancer & Oncology Source Type: research

Cancer-associated mucins: role in immune modulation and metastasis
AbstractMucins (MUC) protect epithelial barriers from environmental insult to maintain homeostasis. However, their aberrant overexpression and glycosylation in various malignancies facilitate oncogenic events from inception to metastasis. Mucin-associated sialyl-Tn (sTn) antigens bind to various receptors present on the dendritic cells (DCs), macrophages, and natural killer (NK) cells, resulting in overall immunosuppression by either receptor masking or inhibition of cytolytic activity. MUC1-mediated interaction of tumor cells with innate immune cells hampers cross-presentation of processed antigens on MHC class I molecule...
Source: Cancer and Metastasis Reviews - January 8, 2019 Category: Cancer & Oncology Source Type: research

Tumor pH and metastasis: a malignant process beyond hypoxia
AbstractTumors often show, compared to normal tissues, a markedly decreased extracellular pH resulting from anaerobic or aerobic glycolysis in combination with a reduced removal of acidic metabolites. Several studies indicate that acidosis induces (independently from hypoxia) hematogenous and lymphatic spread of tumor cells worsening the long-term prognosis of tumor patients. This review gives an overview on the impact of low pH on different steps of metastasis including (a) local tumor cell invasion and angiogenesis, (b) intravasation of tumor cells and detachment into the circulation, and (c) adherence of circulating tum...
Source: Cancer and Metastasis Reviews - January 4, 2019 Category: Cancer & Oncology Source Type: research

Preface
(Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - January 4, 2019 Category: Cancer & Oncology Source Type: research

MACC1 —the first decade of a key metastasis molecule from gene discovery to clinical translation
AbstractDeciphering the paths to metastasis and identifying key molecules driving this process is one important issue for understanding and treatment of cancer. Such a key driver molecule is Metastasis Associated in Colon Cancer 1 (MACC1). A decade long research on this evolutionarily conserved molecule with features of a transcription factor as well as an adapter protein for versatile protein-protein interactions has shown that it has manifold properties driving tumors to their metastatic stage. MACC1 transcriptionally regulates genes involved in epithelial-mesenchymal transition (EMT), including those which are able to d...
Source: Cancer and Metastasis Reviews - January 3, 2019 Category: Cancer & Oncology Source Type: research

Applications of Raman spectroscopy in cancer diagnosis
AbstractNovel approaches toward understanding the evolution of disease can lead to the discovery of biomarkers that will enable better management of disease progression and improve prognostic evaluation. Raman spectroscopy is a promising investigative and diagnostic tool that can assist in uncovering the molecular basis of disease and provide objective, quantifiable molecular information for diagnosis and treatment evaluation. This technique probes molecular vibrations/rotations associated with chemical bonds in a sample to obtain information on molecular structure, composition, and intermolecular interactions. Raman scatt...
Source: Cancer and Metastasis Reviews - December 19, 2018 Category: Cancer & Oncology Source Type: research

Mitochondrial polymorphisms contribute to aging phenotypes in MNX mouse models
AbstractMany inbred strains of mice develop spontaneous tumors as they age. Recent awareness of the impacts of mitochondrial DNA (mtDNA) on cancer and aging has inspired developing a mitochondrial-nuclear exchange (MNX) mouse model in which nuclear DNA is paired with mitochondrial genomes from other strains of mouse. MNX mice exhibit mtDNA influences on tumorigenicity and metastasis upon mating with transgenic mice. However, we also wanted to investigate spontaneous tumor phenotypes as MNX mice age. Utilizing FVB/NJ, C57BL/6J, C3H/HeN, and BALB/cJ wild-type inbred strains, previously documented phenotypes were observed as ...
Source: Cancer and Metastasis Reviews - December 14, 2018 Category: Cancer & Oncology Source Type: research

Roles of the mitochondrial genetics in cancer metastasis: not to be ignored any longer
AbstractMitochondrial DNA (mtDNA) encodes for only a fraction of the proteins that are encoded within the nucleus, and therefore has typically been regarded as a lesser player in cancer biology and metastasis. Accumulating evidence, however, supports an increased role for mtDNA impacting tumor progression and metastatic susceptibility. Unfortunately, due to this delay, there is a dearth of data defining the relative contributions of specific mtDNA polymorphisms (SNP), which leads to an inability to effectively use these polymorphisms to guide and enhance therapeutic strategies and diagnosis. In addition, evidence also sugg...
Source: Cancer and Metastasis Reviews - December 12, 2018 Category: Cancer & Oncology Source Type: research

Tackling tumor heterogeneity and phenotypic plasticity in cancer precision medicine: our experience and a literature review
AbstractThe predominant cause of cancer mortality is metastasis. The major impediment to cancer cure is the intrinsic or acquired resistance to currently available therapies. Cancer is heterogeneous at the genetic, epigenetic, and metabolic levels. And, while a molecular-targeted drug may be pathway-precise, it can still fail to achieve wholesome cancer-precise toxicity. In the current review, we discuss the strategic differences between targeting the strengths of cancer cells in phenotypic plasticity and heterogeneity and targeting shared vulnerabilities of cancer cells such as the compromised integrity of membranous orga...
Source: Cancer and Metastasis Reviews - November 27, 2018 Category: Cancer & Oncology Source Type: research

Cancer-associated fibroblasts as key regulators of the breast cancer tumor microenvironment
AbstractTumor cells exist in close proximity with non-malignant cells. Extensive and multilayered crosstalk between tumor cells and stromal cells tailors the tumor microenvironment (TME) to support survival, growth, and metastasis. Fibroblasts are one of the largest populations of non-malignant host cells that can be found within the TME of breast, pancreatic, and prostate tumors. Substantial scientific evidence has shown that these cancer-associated fibroblasts (CAFs) are not only associated with tumors by proximity but are also actively recruited to developing tumors where they can influence other cells of the TME as wel...
Source: Cancer and Metastasis Reviews - November 21, 2018 Category: Cancer & Oncology Source Type: research

Metabolic reprogramming of mitochondrial respiration in metastatic cancer
AbstractTumor initiation, progression, and metastasis are tissue context-dependent processes. Cellular and non-cellular factors provide the selective microenvironment that determines the fate of the evolving tumor through mechanisms that include metabolic reprogramming. Genetic and epigenetic changes contribute to this reprogramming process, which is orchestrated through ongoing communication between the mitochondrial and nuclear genomes. Metabolic flexibility, in particular the ability to rapidly adjust the balance between glycolytic and mitochondrial energy production, is a hallmark of aggressive, invasive, and metastati...
Source: Cancer and Metastasis Reviews - November 17, 2018 Category: Cancer & Oncology Source Type: research

Perspectives on the role of brain cellular players in cancer-associated brain metastasis: translational approach to understand molecular mechanism of tumor progression
AbstractBrain metastasis is one of the leading causes of death among cancer patients. Cancer cells migrate to various sites and harbor different niche in the body which help cancer cells in their survival. The brain is one of the safest place where cancer cells are protected from immune cells. Breast, lung, and melanoma cancer cells have high propensity to migrate towards the brain. To enter the brain, cancer cells have to cross the blood brain barrier. Survival and finding new niche in the brain are directed by several mechanisms in which different cellular players take part such as astrocytes, microglia, Schwann cells, s...
Source: Cancer and Metastasis Reviews - October 4, 2018 Category: Cancer & Oncology Source Type: research

A contemporary review of male breast cancer: current evidence and unanswered questions
AbstractMale breast cancer is rare, accounting for 1% of all breast cancer diagnoses in the USA. Because of its rarity, most major breast cancer trials have included only female patients. This has resulted in limited prospective data to guide the clinical management of men with breast cancer. As a result, treatment decisions are typically extrapolated from data generated in female patients. This approach may be suboptimal, particularly considering the differing hormonal milieus between men and women with respect to both breast cancer development and treatment. Herein, we summarize current knowledge of the biology and clini...
Source: Cancer and Metastasis Reviews - September 19, 2018 Category: Cancer & Oncology Source Type: research

Pleiotropic effects of moonlighting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cancer progression, invasiveness, and metastases
AbstractGlyceraldehyde-3-phosphate dehydrogenase (GAPDH) may represent the quintessential example of a moonlighting protein. The latter are a new, intriguing class of cell proteins which exhibit multiple activities in different subcellular locales apart from their initially, well-characterized function. As such, apart from its classical role in energy production, membrane-bound GAPDH is required for membrane fusion, endocytosis and, intriguingly, for iron transport. Cytoplasmic GAPDH regulates mRNA stability and is required for ER to Golgi trafficking. Nuclear GAPDH is involved in apoptosis, transcriptional gene regulation...
Source: Cancer and Metastasis Reviews - September 12, 2018 Category: Cancer & Oncology Source Type: research

Cross-talk between lung cancer and bones results in neutrophils that promote tumor progression
This study identifies novel cellular targets for lung cancer treatment. Here, we summarize and evaluate recent advances in our understanding of lung tumor microenvironment. (Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - September 10, 2018 Category: Cancer & Oncology Source Type: research

Cancers of the eye
AbstractOcular cancers are unique among the diseases of the eye, threatening both vision and life. In most cases, the diagnosis can be made utilizing a careful clinical history and specialized ocular examination. Eye cancer diagnosis relies heavily on imaging techniques such as high-frequency ultrasound, fluorescein angiography, anterior and posterior segment optical coherence tomography, computed tomography (CT), and magnetic resonance imaging (MRI). Once the diagnosis is established, treatment decisions depend on the tumor ’s location, size, local extension, patterns of growth, and secondary complications. Treatmen...
Source: Cancer and Metastasis Reviews - September 10, 2018 Category: Cancer & Oncology Source Type: research

Cross-talk between lung cancer and bones results in neutrophils that promote tumor progression
This study identifies novel cellular targets for lung cancer treatment. Here, we summarize and evaluate recent advances in our understanding of lung tumor microenvironment. (Source: Cancer and Metastasis Reviews)
Source: Cancer and Metastasis Reviews - September 10, 2018 Category: Cancer & Oncology Source Type: research

Cancers of the eye
AbstractOcular cancers are unique among the diseases of the eye, threatening both vision and life. In most cases, the diagnosis can be made utilizing a careful clinical history and specialized ocular examination. Eye cancer diagnosis relies heavily on imaging techniques such as high-frequency ultrasound, fluorescein angiography, anterior and posterior segment optical coherence tomography, computed tomography (CT), and magnetic resonance imaging (MRI). Once the diagnosis is established, treatment decisions depend on the tumor ’s location, size, local extension, patterns of growth, and secondary complications. Treatmen...
Source: Cancer and Metastasis Reviews - September 10, 2018 Category: Cancer & Oncology Source Type: research