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Cancer Metastasis Reviews

Jianrong Lu
The 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 PGC1α transcriptional coactivator is a central coordinator of oxidative metabolism...
April 17, 2019: Cancer Metastasis Reviews
Katharine A White, Kyle Kisor, Diane L Barber
An 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...
April 13, 2019: Cancer Metastasis Reviews
Smitha R Pillai, Mehdi Damaghi, Yoshinori Marunaka, Enrico Pierluigi Spugnini, Stefano Fais, Robert J Gillies
While 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 evidence 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 "aerobic glycolysis" or the "Warburg Effect...
March 26, 2019: Cancer Metastasis Reviews
Samata Kakkad, Balaji Krishnamachary, Desmond Jacob, Jesus Pacheco-Torres, Eibhlin Goggins, Santosh Kumar Bharti, Marie-France Penet, Zaver M Bhujwalla
Hypoxia 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...
March 6, 2019: Cancer Metastasis Reviews
Sofia Avnet, Gemma Di Pompo, Silvia Lemma, Nicola Baldini
Skeletal 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 both organic and hard inorganic matrices and bone cells are used to sense protons and adapt or react to a low pH to maintain tissue homeostasis...
March 2, 2019: Cancer Metastasis Reviews
Valéry L Payen, Luca X Zampieri, Paolo E Porporato, Pierre Sonveaux
In 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...
March 1, 2019: Cancer Metastasis Reviews
Arig Ibrahim-Hashim, Veronica Estrella
The 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...
February 26, 2019: Cancer Metastasis Reviews
Anna Bång-Rudenstam, Myriam Cerezo-Magaña, Mattias Belting
Although 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 and how these pathways may constitute potential Achilles' heels of the cancer cell machinery and alternative treatment targets of metastasis...
February 15, 2019: Cancer Metastasis Reviews
Annasofia Anemone, Lorena Consolino, Francesca Arena, Martina Capozza, Dario Livio Longo
Cancer cells are characterized by a metabolic shift in cellular energy production, orchestrated by the transcription factor HIF-1α, 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 spatial distribution of tumor pHe...
February 14, 2019: Cancer Metastasis Reviews
Liu Yang, Xiaoge Hu, Yin-Yuan Mo
The 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...
February 7, 2019: Cancer Metastasis Reviews
Mariantonia Logozzi, Enrico Spugnini, Davide Mizzoni, Rossella Di Raimo, Stefano Fais
The 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...
February 4, 2019: Cancer Metastasis Reviews
Ebbe Boedtkjer
Cell 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...
February 4, 2019: Cancer Metastasis Reviews
Pawel Swietach
Metabolism 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 alteration...
February 1, 2019: Cancer Metastasis Reviews
(no author information available yet)
No abstract text is available yet for this article.
January 25, 2019: Cancer Metastasis Reviews
Ian S Reynolds, Michael Fichtner, Deborah A McNamara, Elaine W Kay, Jochen H M Prehn, John P Burke
Overexpression 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 clonogenicity in vitro as well as tumor growth, tumorigenicity, and metastasis in 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 association between mucin glycoproteins with apoptosis, cell growth, invasion, migration, adhesion, and clonogenicity in vitro as well as tumor growth, tumorigenicity, and metastasis in vivo in epithelial-derived cancers...
January 24, 2019: Cancer Metastasis Reviews
Rakesh Bhatia, Shailendra K Gautam, Andrew Cannon, Christopher Thompson, Bradley R Hall, Abhijit Aithal, Kasturi Banerjee, Maneesh Jain, Joyce C Solheim, Sushil Kumar, Surinder K Batra
Mucins (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 molecules...
January 8, 2019: Cancer Metastasis Reviews
Oliver Thews, Anne Riemann
Tumors 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 tumor cells, transmigration and invasion in the new host tissue...
January 4, 2019: Cancer Metastasis Reviews
Stephanie Tucker
No abstract text is available yet for this article.
January 4, 2019: Cancer Metastasis Reviews
Harikrishnan Radhakrishnan, Wolfgang Walther, Fabian Zincke, Dennis Kobelt, Francesca Imbastari, Müge Erdem, Benedikt Kortüm, Mathias Dahlmann, Ulrike Stein
Deciphering 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 directly induce metastasis like c-MET, impacts tumor cell migration and invasion, and induces metastasis in solid cancers...
January 3, 2019: Cancer Metastasis Reviews
Gregory W Auner, S Kiran Koya, Changhe Huang, Brandy Broadbent, Micaela Trexler, Zachary Auner, Angela Elias, Katlyn Curtin Mehne, Michelle A Brusatori
Novel 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...
December 19, 2018: Cancer Metastasis Reviews
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