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EMT metabolism

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https://www.readbyqxmd.com/read/28219702/genetic-alterations-in-krebs-cycle-and-its-impact-on-cancer-pathogenesis
#1
REVIEW
Karishma Sajnani, Farhadul Islam, Robert Anthony Smith, Vinod Gopalan, Alfred King-Yin Lam
Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and citrate synthase are noted in many cancers...
February 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28202352/amino-acid-transporter-slc38a3-promotes-metastasis-of-non-small-cell-lung-cancer-cells-by-activating-pdk1
#2
Yanhui Wang, Li Fu, Minqing Cui, Yongbin Wang, Yan Xu, Molin Li, Jun Mi
BACKGROUND: Tumor metastasis is a finely-tuned pathological process coupled to metabolic reprogramming that includes both glutamine and glucose. The solute carrier SLC38A3, a member of amino acid/polyamine/organocation (APC) superfamily, is an l-glutamine transporter. It is not clear whether SLC38A3 involves the metastasis of NSCLC (non small cell lung cancer). METHODS: The scratch test and transwell assay were used to determine the ability of NSCLC to migrate. Cellular amino acids content was determined by mass spectrometry...
February 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28195146/the-inhibition-of-lung-cancer-cell-migration-by-ahr-regulated-autophagy
#3
Chi-Hao Tsai, Ching-Hao Li, Yu-Wen Cheng, Chen-Chen Lee, Po-Lin Liao, Cheng-Hui Lin, Shih-Hsuan Huang, Jaw-Jou Kang
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in multiple organs and tissues. Whereas AhR mediates the metabolism of xenobiotic and endogenous compounds, its novel function in cancer epithelial-mesenchymal transition (EMT) remains controversial. Autophagy also participates in tumour progression through its functions in cell homeostasis and facilitates adaptation to EMT progression. In the present study, we found that AhR-regulated autophagy positively modulates EMT in non-small cell lung cancer cells...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28176759/snail-reprograms-glucose-metabolism-by-repressing-phosphofructokinase-pfkp-allowing-cancer-cell-survival-under-metabolic-stress
#4
Nam Hee Kim, Yong Hoon Cha, Jueun Lee, Seon-Hyeong Lee, Ji Hye Yang, Jun Seop Yun, Eunae Sandra Cho, Xianglan Zhang, Miso Nam, Nami Kim, Young-Su Yuk, So Young Cha, Yoonmi Lee, Joo Kyung Ryu, Sunghyouk Park, Jae-Ho Cheong, Sang Won Kang, Soo-Youl Kim, Geum-Sook Hwang, Jong In Yook, Hyun Sil Kim
Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial-mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of phosphofructokinase, platelet (PFKP), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis...
February 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28161638/6-phosphofructo-2-kinase-fructose-2-6-bisphosphatase-3-is-required-for-transforming-growth-factor-%C3%AE-1-enhanced-invasion-of-panc1-cells-in%C3%A2-vitro
#5
Abdullah Yalcin, Tugba H Solakoglu, Selahattin C Ozcan, Saime Guzel, Sabire Peker, Serap Celikler, Basak D Balaban, Elif Sevinc, Yunus Gurpinar, Jason A Chesney
Transforming growth factor β1 (TGFβ1) is a well-established inducer of the epithelial-mesenchymal transition (EMT) that is essential for the acquisition of malignant properties, such as invasion, in tumor cells. Although recent studies suggest that the EMT in tumor cells is associated with reprogramming of energy metabolism and TGFβ1 has been shown to stimulate glycolysis in multiple primary cell lines, little is known about TGFβ1's effect on glycolysis and glycolytic regulators in transformed cells. Given the known regulatory role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase-3 (PFKFB3) in glycolysis and association of glycolytic activity with malignant features such as invasion, we sought to investigate whether TGFβ1 regulates PFKFB3 expression and if PFKFB3 is involved in the TGFβ1-mediated increase in the invasive ability of the Panc1 cell cline-a well-established model of TGFβ1-initiated EMT...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28158294/deep-proteome-mapping-of-wm-266-4-human-metastatic-melanoma-cells-from-oncogenic-addiction-to-druggable-targets
#6
Eumorphia G Konstantakou, Athanassios D Velentzas, Athanasios K Anagnostopoulos, Zoi I Litou, Ourania A Konstandi, Aikaterini F Giannopoulou, Ema Anastasiadou, Gerassimos E Voutsinas, George Th Tsangaris, Dimitrios J Stravopodis
Cutaneous melanoma is a malignant tumor of skin melanocytes that are pigment-producing cells located in the basal layer (stratum basale) of epidermis. Accumulation of genetic mutations within their oncogenes or tumor-suppressor genes compels melanocytes to aberrant proliferation and spread to distant organs of the body, thereby resulting in severe and/or lethal malignancy. Metastatic melanoma's heavy mutational load, molecular heterogeneity and resistance to therapy necessitate the development of novel biomarkers and drug-based protocols that target key proteins involved in perpetuation of the disease...
2017: PloS One
https://www.readbyqxmd.com/read/28137309/induction-of-metastasis-cancer-stem-cell-phenotype-and-oncogenic-metabolism-in-cancer-cells-by-ionizing-radiation
#7
REVIEW
Su Yeon Lee, Eui Kyong Jeong, Min Kyung Ju, Hyun Min Jeon, Min Young Kim, Cho Hee Kim, Hye Gyeong Park, Song Iy Han, Ho Sung Kang
Radiation therapy is one of the major tools of cancer treatment, and is widely used for a variety of malignant tumours. Radiotherapy causes DNA damage directly by ionization or indirectly via the generation of reactive oxygen species (ROS), thereby destroying cancer cells. However, ionizing radiation (IR) paradoxically promotes metastasis and invasion of cancer cells by inducing the epithelial-mesenchymal transition (EMT). Metastasis is a major obstacle to successful cancer therapy, and is closely linked to the rates of morbidity and mortality of many cancers...
January 30, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28089831/monomethyltransferase-setd8-regulates-breast-cancer-metabolism-via-stabilizing-hypoxia-inducible-factor-1%C3%AE
#8
Run Huang, Yang Yu, Xiangyun Zong, Xiaolin Li, Lisi Ma, Qi Zheng
SETD8 is a methyltransferase that specifically catalyzes the monomethylation of lysine 20 on histone H4. Previous studies have demonstrated that SETD8 is associated with proper cell cycle progression, DNA damage response, and transcriptional regulation. A recent study revealed that SETD8 played an important role in epithelial-mesenchymal transition (EMT) in association with TWIST and enhanced metastatic potential of breast cancer cells. However, the contribution of SETD8 to metabolism reprogramming, one hallmark of cancer, has never been reported...
April 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28089517/hypoxia-induces-a-hif-1-dependent-transition-from-collective-to-amoeboid-dissemination-in-epithelial-cancer-cells
#9
Steffi Lehmann, Veronika Te Boekhorst, Julia Odenthal, Roberta Bianchi, Sjoerd van Helvert, Kristian Ikenberg, Olga Ilina, Szymon Stoma, Jael Xandry, Liying Jiang, Reidar Grenman, Markus Rudin, Peter Friedl
Cancer metastases arise from a multi-step process that requires metastasizing tumor cells to adapt to signaling input from varying tissue environments [1]. As an early metastatic event, cancer cell dissemination occurs through different migration programs, including multicellular, collective, and single-cell mesenchymal or amoeboid migration [2-4]. Migration modes can interconvert based on changes in cell adhesion, cytoskeletal mechanotransduction [5], and/or proteolysis [6], most likely under the control of transcriptional programs such as the epithelial-to-mesenchymal transition (EMT) [7, 8]...
February 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28059830/2-deoxy-d-glucose-suppresses-the-migration-and-reverses-the-drug-resistance-of-colon-cancer-cells-through-adam-expression-regulation
#10
Ga B Park, Yoon H Chung, Daejin Kim
Cancer cell resistance to chemotherapy is associated with a poor prognosis. The compound 2-deoxy-D-glucose (2-DG) enhances the effect of chemotherapy against cancer cells lines in vitro and in vivo. However, its effect on the epithelial to mesenchymal transition (EMT) in drug-resistant cancer cells has not been fully elucidated. In this study, we investigated whether treatment of 5-fluorouracil or oxaliplatin-resistant colorectal cancer (CRC) cells with 2-DG suppressed their migratory activity and enhanced their susceptibility to chemotherapy...
January 2, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28030815/a-novel-non-canonical-wnt-signature-for-prostate-cancer-aggressiveness
#11
Elise Sandsmark, Ailin Falkmo Hansen, Kirsten M Selnæs, Helena Bertilsson, Anna M Bofin, Alan J Wright, Trond Viset, Elin Richardsen, Finn Drabløs, Tone F Bathen, May-Britt Tessem, Morten B Rye
Activation of the Canonical Wnt pathway (CWP) has been linked to advanced and metastatic prostate cancer, whereas the Wnt5a-induced non-canonical Wnt pathway (NCWP) has been associated with both good and poor prognosis. A newly discovered NCWP, Wnt5/Fzd2, has been shown to induce epithelial-to-mesenchymal transition (EMT) in cancers, but has not been investigated in prostate cancer. The aim of this study was to investigate if the CWP and NCWP, in combination with EMT, are associated with metabolic alterations, aggressive disease and biochemical recurrence in prostate cancer...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28011713/germline-compound-heterozygous-poly-glutamine-deletion-in-usf3-may-be-involved-in-predisposition-to-heritable-and-sporadic-epithelial-thyroid-carcinoma
#12
Ying Ni, Spencer Seballos, Benjamin Fletcher, Todd Romigh, Lamis Yehia, Jessica Mester, Leigha Senter, Farshad Niazi, Motoyasu Saji, Matthew D Ringel, Thomas LaFramboise, Charis Eng
Cowden syndrome (CS) is an autosomal dominant disorder that predisposes to breast, thyroid, and other epithelial cancers. Differentiated thyroid carcinoma (DTC), as one of the major component cancers of CS, is the fastest rising incident cancer in the USA, and the most familial of all solid tumours. To identify additional candidate genes of CS and potentially DTC, we analysed a multi-generation CS-like family with papillary thyroid cancer (PTC), applying a combined linkage-based and whole-genome sequencing strategy and identified an in-frame germline compound heterozygous deletion, p...
December 22, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28000883/2-methoxyestradiol-inhibits-the-proliferation-and-migration-and-reduces-the-radioresistance-of-nasopharyngeal-carcinoma-cne-2-stem-cells-via-nf-%C3%AE%C2%BAb-hif-1-signaling-pathway-inactivation-and-emt-reversal
#13
Shun-Long Wu, Ya-Jun Li, Kui Liao, Lei Shi, Na Zhang, Shuang Liu, Yao-Yao Hu, Shao-Lin Li, Ying Wang
Accumulating evidence indicates that cancer stem cells (CSCs) are a source of resistance to radiation therapy (RT); however, the mechanism of this resistance remains unclear. 2-Methoxyestradiol (2-ME2) is a metabolic product of estrogen in the body. Recent studies have found that 2-ME2 regulates the activation of transcription factors, including nuclear factor (NF)-κB/hypoxia-inducible factor-1 (HIF-1), thus contributing to tumor cell apoptosis and chemosensitivity. Therefore, 2-ME2 is being studied as a potential anticancer drug...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/27999314/molecular-mechanisms-and-metabolomics-of-natural-polyphenols-interfering-with-breast-cancer-metastasis
#14
REVIEW
Yingqian Ci, Jinping Qiao, Mei Han
Metastatic cancers are the main cause of cancer-related death. In breast primary cancer, the five-year survival rate is close to 100%; however, for metastatic breast cancer, that rate drops to a mere 25%, due in part to the paucity of effective therapeutic options for treating metastases. Several in vitro and in vivo studies have indicated that consumption of natural polyphenols significantly reduces the risk of cancer metastasis. Therefore, this review summarizes the research findings involving the molecular mechanisms and metabolomics of natural polyphenols and how they may be blocking breast cancer metastasis...
December 17, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27986567/irisin-suppresses-the-migration-proliferation-and-invasion-of-lung-cancer-cells-via-inhibition-of-epithelial-to-mesenchymal-transition
#15
Lei Shao, Huanjie Li, Jian Chen, Haibo Song, Yuzhu Zhang, Fei Wu, Wenjuan Wang, Wen Zhang, Fang Wang, Hui Li, Dongqi Tang
Irisin is involved in promoting metabolism, immune regulation, and affects chronic inflammation in many systemic diseases, including gastric cancer. However, the role of irisin in lung cancer is not well characterized. To determine whether irisin has a protective effect against lung cancer, we cultured A549 and NCI-H446 lung cancer cells and treated them with irisin. We detected the proliferation by MTT assay, and assessed the migration and invasion of the cells by scratch wound healing assay and Tran-swell assay...
December 13, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27939360/cellular-and-molecular-mechanisms-underlying-alcohol-induced-aggressiveness-of-breast-cancer
#16
REVIEW
Yongchao Wang, Mei Xu, Zun-Ji Ke, Jia Luo
Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors...
January 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27926487/egf-induces-epithelial-mesenchymal-transition-and-cancer-stem-like-cell-properties-in-human-oral-cancer-cells-via-promoting-warburg-effect
#17
Qilin Xu, Qunzhou Zhang, Yasutaka Ishida, Souren Hajjar, Xudong Tang, Haoran Shi, Chi V Dang, Anh D Le
"Warburg effect", the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24- population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/27878251/glyceraldehyde-3-phosphate-dehydrogenase-promotes-cancer-growth-and-metastasis-through-upregulation-of-snail-expression
#18
Kaiyan Liu, Zhenjie Tang, Amin Huang, Ping Chen, Panpan Liu, Jing Yang, Wenhua Lu, Jianwei Liao, Yicheng Sun, Shijun Wen, Yumin Hu, Peng Huang
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in multiple cellular functions including metabolism and gene transcription. Our previous study showed that GAPDH expression was elevated in colon cancer and further upregulated in liver metastatic tissues, suggesting a possilbe role of GAPDH in promoting cancer metastasis. The present study was designed to investigate the underlying mechanism, using multiple experimental approaches including genetic silencing of GAPDH expression by short hairpin RNA (shRNA) and biochemcial/molecular analyses of the key events involved in glycolytic metabolism and epithelial-mesenchymal transition (EMT)...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27869167/cystine-addiction-of-triple-negative-breast-cancer-associated-with-emt-augmented-death-signaling
#19
X Tang, C-K Ding, J Wu, J Sjol, S Wardell, I Spasojevic, D George, D P McDonnell, D S Hsu, J T Chang, J-T Chi
Despite the advances in the diagnosis and treatment of breast cancer, breast cancers still cause significant mortality. For some patients, especially those with triple-negative breast cancer, current treatments continue to be limited and ineffective. Therefore, there remains an unmet need for a novel therapeutic approach. One potential strategy is to target the altered metabolic state that is rewired by oncogenic transformation. Specifically, this rewiring may render certain outside nutrients indispensable...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27865365/implications-of-cancer-stem-cells-in-developing-therapeutic-resistance-in-oral-cancer
#20
REVIEW
Prajna Paramita Naik, Durgesh Nandini Das, Prashanta Kumar Panda, Subhadip Mukhopadhyay, Niharika Sinha, Prakash Priyadarshi Praharaj, Rajesh Agarwal, Sujit Kumar Bhutia
Conventional therapeutics are often frequented with recurrences, refraction and regimen resistance in oral cavity cancers which are predominantly manifested by cancer stem cells (CSCs). During oncoevolution, cancer cells may undergo structural and functional reprogramming wherein they evolve as highly tolerant CSC phenotypes with greater survival advantages. The CSCs possess inherent and exclusive properties including self-renewal, hierarchical differentiation, and tumorigenicity that serve as the basis of chemo-radio-resistance in oral cancer...
November 2016: Oral Oncology
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