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https://www.readbyqxmd.com/read/28544627/epithelial-to-mesenchymal-transition-transcription-factors-in-cancer-associated-fibroblasts
#1
REVIEW
Josep Baulida
Beyond inducing epithelial-to-mesenchymal transcription (EMT), transcriptional factors of the Snail, ZEB and Twist families (EMT-TFs) control global plasticity programs affecting cell stemness and fate. Literature addressing the reactivation of these factors in adult tumour cells is very extensive, as they enable cancer cell plasticity and fuel both tumour initiation and metastatic spread. Incipient data reveal that EMT-TFs are also expressed in fibroblasts, providing these with additional properties. Here, I will review recent reports on the expression of EMT-TFs in cancer-associated fibroblasts (CAFs)...
May 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28543447/fas-signaling-induces-stemness-properties-in-colorectal-cancer-by-regulation-of-bmi1
#2
Jiaxuan Chen, Yadong Wang, Linghao Zhuo, Zhizhong Liu, Tao Liu, Wenjing Li, Yidong Cai, Haoxuan Zheng
Fas signaling promotes colorectal cancer (CRC) metastasis by inducing epithelial- mesenchymal transition (EMT). The acquisition of EMT properties in turn induces stemness but the mechanism by which Fas signaling contributes to it still remains unclear. Hence, the aim of this study was to investigate how Fas signaling regulates CRC stemness. For this purpose, soft agar assay, sphere formation assay, cell survival analysis, immunoblot, qRT-PCR, chromatin immunoprecipitation, and luciferase reporter assay were performed...
May 25, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28542577/leptin-signals-via-tgfb1-to-promote-metastatic-potential-and-stemness-in-breast-cancer
#3
Ameet K Mishra, Christopher R Parish, Ma-Li Wong, Julio Licinio, Anneke C Blackburn
Epidemiological studies have shown obesity to be linked with poorer outcomes in breast cancer patients. The molecular mechanisms responsible for the increased risk of invasive/metastatic disease with obesity are complex, but may include elevated levels of adipokines such as leptin. Using physiological levels of leptin found in obesity in a novel chronic in vitro treatment model (≤200 ng/ml for 14 days), we confirmed the occurrence of leptin-mediated changes in growth, apoptosis and metastatic behavior, and gene expression changes representing epithelial-to-mesenchymal transition (EMT) and a cancer stem cell (CSC) like phenotype in breast epithelial and cancer cell lines (MCF10A, MCF10AT1, MCF7 and MDA-MB-231)...
2017: PloS One
https://www.readbyqxmd.com/read/28542126/human-mscs-promotes-colorectal-cancer-epithelial-mesenchymal-transition-and-progression-via-ccl5-%C3%AE-catenin-slug-pathway
#4
Ke Chen, Qianqian Liu, Lai Ling Tsang, Qiao Ye, Hsiao Chang Chan, Yunwei Sun, Xiaohua Jiang
Mesenchymal stem cells (MSCs) extensively interact with cancer cells and other stroma cells in the tumor microenvironment. However, the role of MSCs in colorectal cancer (CRC) progression and metastasis is controversial. This study was designed to identify the role of inflammation-activated-MSCs in CRC development. Our results show that tumor necrosis factor (TNF)-α-preactivated-hMSCs significantly promote the progression of colon cancer cells by enhancing cell proliferation, epithelial-mesenchymal transition, migration, and invasion...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28536011/tg737-regulates-epithelial-mesenchymal-transition-and-cancer-stem-cell-properties-via-a-negative-feedback-circuit-between-snail-and-hnf4%C3%AE-during-liver-stem-cell-malignant-transformation
#5
Qike Huang, Meng Pu, Ge Zhao, Bin Dai, Zhenyuan Bian, Haili Tang, Chong Chen, Wei Liu, Xuan Qu, Liangliang Shen, Kaishan Tao
Determining the origin of liver cancer stem cells is important for treating hepatocellular carcinoma. Tg737 deficiency plays an important role in the malignant transformation of liver stem cells, but the underlying mechanism remains unclear. Here we established a chemical-induced mouse hepatoma model and found that Tg737 and hepatocyte nuclear factor 4-alpha (HNF4α) expression decreased and epithelial-mesenchymal transition (EMT)-related marker expression increased during liver cancer development. To investigate the underlying mechanism, we knocked down Tg737 in WB-F344 (WB) rat hepatic oval cells...
May 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28534939/mir%C3%A2-181b%C3%A2-5p-mediates-tgf%C3%A2-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-non-small-cell-lung-cancer-stem-like-cells-derived-from-lung-adenocarcinoma-a549-cells
#6
Xuetao Li, Jing Han, Haizhen Zhu, Lina Peng, Zhengtang Chen
The ability of non-small cell lung cancer (NSCLC) cells to invade and metastasize is associated with epithelial-to-mesenchymal transition (EMT). The process of EMT is, at least in part, regulated by microRNAs. However, it is unknown whether microRNAs regulate EMT in cancer stem-like cells (CSLCs), or which microRNAs are involved. In the present study, we compared microRNA expression in A549 cells, TGF‑β1-treated A549 cells, CSLCs characterized by the CD133+/CD326+ phenotype, and TGF‑β1-treated CSLCs. We found that miR‑181b‑5p expression was upregulated by TGF‑β1...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28532298/ctbp-an-emerging-oncogene-and-novel-small-molecule-drug-target-advances-in-the-understanding-of-its-oncogenic-action-and-identification-of-therapeutic-inhibitors
#7
M Michael Dcona, Benjamin L Morris, Keith C Ellis, Steven R Grossman
C-terminal Binding Proteins (CtBP) 1 and 2 are oncogenic transcriptional co-regulators overexpressed in many cancer types, with their expression level correlating to worse prognostic outcomes and aggressive tumor features. CtBP negatively regulates the expression of many tumor suppressor genes, while coactivating genes that promote proliferation, epithelial-mesenchymal transition, and cancer stem cell self-renewal activity. In light of this evidence, the development of novel inhibitors that mitigate CtBP function may provide clinically actionable therapeutic tools...
May 22, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28529586/immunohistochemical-analysis-of-nanog-expression-and-epithelial-mesenchymal-transition-in-pulmonary-sarcomatoid-carcinoma
#8
Takeshi Tamaki, Toshiki Shimizu, Maiko Niki, Michiomi Shimizu, Tohru Nishizawa, Shosaku Nomura
Pulmonary sarcomatoid carcinomas (PSCs) are defined as a group of poorly differentiated non-small cell lung cancers that demonstrate sarcoma-like differentiation. The mechanism of mesenchymal differentiation in PSC is epithelial-mesenchymal transition (EMT). The expression of homeobox protein NANOG (NANOG), which regulates the pluripotency of embryonic stem cells, is associated with the EMT process. Therefore, the present study aimed to assess the expression level of NANOG and the status of the EMT process in PSC...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529570/the-meaning-of-piwi-proteins-in-cancer-development
#9
Monika Litwin, Anna Szczepańska-Buda, Aleksandra Piotrowska, Piotr Dzięgiel, Wojciech Witkiewicz
Cancer is a histologically and genetically heterogeneous population of tumor cells that exhibits distinct molecular profiles determined by epigenetic alterations. P-element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) have been previously demonstrated to be involved in epigenetic regulation in germline cells. Recently, reactivation of PIWI expression, primarily PIWI-like protein 1 and 2, through aberrant DNA methylation resulting in genomic silencing has been identified in various types of tumors...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529105/psme3-induces-epithelial-mesenchymal-transition-with-inducing-the-expression-of-csc-markers-and-immunosuppression-in-breast-cancer
#10
Ziying Yi, Dejuan Yang, Xuelian Liao, Fuchun Guo, Yongsheng Wang, Xiaoyi Wang
Proteasome activator subunit 3 (PSME3) plays a key role in breast cancer by regulating the cell cycle. However, its role in other pathogenesis-related features of breast cancer is unclear. In this study, we found that overexpression of PSME3 induced the epithelial-mesenchymal transition and contributed to induce the expression of cancer stem cell markers of the MDA-MB-231 cell line, thus increasing the migration, and invasion of the cells. Moreover, overexpression of PSME3 reduced the chemotaxis of CD8(+) T cells and induced the apoptosis of T cells in vitro...
May 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28529067/immunoproapoptotic-molecule-scfv-fdt-tbid-modified-mesenchymal-stem-cells-for-prostate-cancer-dual-targeted-therapy
#11
Fengqi Yan, Xia Li, Nan Li, Rui Zhang, Qinhao Wang, Yi Ru, Xiaoke Hao, Jianxin Ni, He Wang, Guojun Wu
Highly efficient target therapy is urgently needed for prostate cancer with overexpression of γ-seminoprotein (γ-SM). Recent studies indicated that mesenchymal stem cells (MSCs) are attractive candidate for cell-based, targeted therapy due to their tumor tropism. Here we designed a dual-target therapeutic system in which MSCs were engineered to produce and deliver scFv-Fdt-tBid, a novel γ-SM-targeted immunoproapoptotic molecule. Such engineered MSCs (MSC.scFv-Fdt-tBid) would home to tumor sites and release the fusion protein to induce the apoptosis of prostate cancer cells...
May 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28526992/epithelial-mesenchymal-transition-emt-in-metastatic-breast-cancer-in-omani-women
#12
Ritu Lakhtakia, Adil Aljarrah, Muhammad Furrukh, Shyam S Ganguly
Breast cancer (BC) in Oman affects younger women and has a more aggressive course. Clinical and biological variables like age, pregnancy, tumor size, type, grade, receptor expression and proliferation predict disease aggression but there is no direct predictor of metastasis except lymphovascular invasion. Epithelial-mesenchymal transition (EMT) is characterized by epithelial cells losing epithelial and acquiring mesenchymal morpho-immunophenotypic characteristics. In tumors, EMT-like transitions may signify a metastatic phenotype and have features in common with cancer stem cells (CSC) which show resistance to chemotherapy...
May 19, 2017: Cancer Microenvironment: Official Journal of the International Cancer Microenvironment Society
https://www.readbyqxmd.com/read/28525366/mesenchymal-stem-cell-carriers-enhance-antitumor-efficacy-of-oncolytic-adenoviruses-in-an-immunocompetent-mouse-model
#13
Esther Rincón, Teresa Cejalvo, Deepak Kanojia, Arantzazu Alfranca, Miguel Ángel Rodríguez-Milla, Raul Andrés Gil Hoyos, Yu Han, Lingjiao Zhang, Ramón Alemany, Maciej S Lesniak, Javier García-Castro
Oncolytic virotherapy represents a promising alternative for cancer treatment; however, viral delivery to the tumor represents a major challenge. Mesenchymal stem cells (MSCs) chemotax to tumors, and can serve as a viral delivery tool. Previously, we demonstrated antitumor therapeutic efficacy for mesenchymal stem cells (MSCs) infected with the oncolytic human adenovirus ICOVIR5 (Celyvir) for treatment of neuroblastoma patients. Given the lack of suitable immunocompetent preclinical models, the mechanism underlying Celyvir antitumor activity remains unknown...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28523512/reduced-adipogenesis-after-lung-tumor-exosomes-priming-in-human-mesenchymal-stem-cells-via-tgf%C3%AE-signaling-pathway
#14
Shihua Wang, Xiaoxia Li, Meiqian Xu, Jing Wang, Robert Chunhua Zhao
A key feature of cancer cachexia is the loss of adipose tissue, mainly due to increased lipolysis and an impairment of adipogenesis. Recent findings have shown that cancer exosomes promoted lipolysis in adipose tissue. However, effects of cancer exosomes on adipogenesis were not reported. In this study, we found that lung cancer exosomes could be internalized by human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) and significantly inhibited hAD-MSC adipogenesis as demonstrated by Oil Red O staining and decreased expression of adipogenic-specific genes...
May 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28522590/notch-inhibitor-pf-03084014-inhibits-hepatocellular-carcinoma-growth-and-metastasis-via-suppression-of-cancer-stemness-due-to-reduced-activation-of-notch1-stat3
#15
Chuan Xing Wu, Aimin Xu, Cathy C Zhang, Peter Olson, Lin Chen, Terence K Lee, Tan To Cheung, Chung Mau Lo, Xiao Qi Wang
Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma (HCC), indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084014 in HCC. HCC spherical cells (stem-like cancer cells), a sphere-derived orthotopic tumor model and one patient-derived xenograft (PDX) model were used in our experiment. We demonstrated that PF-03084014 inhibited the self-renewal and proliferation of cancer stem cells...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522553/glioblastoma-derived-cells-in-vitro-unveil-the-spectrum-of-drug-resistance-capabilty-comparative-study-of-tumour-chemosensitivity-in-different-culture-systems
#16
Monika Witusik-Perkowska, Magdalena Zakrzewska, Beata Sikorska, Wielislaw Papierz, Dariusz J Jaskolski, Janusz Szemraj, Pawel P Liberski
Resistance to cancer drugs is a complex phenomenon which could be influenced by in vitro conditions. However, tumour-derived cell cultures are routinely used for studies related to mechanisms of drug responsiveness or the search for new therapeutic approaches. The purpose of our work was to identify the potential differences in drug resistance and response to treatment of glioblastoma with the use of three in vitro models: traditional adherent culture, serum-free spheroid culture and novel adherent serum-free culture...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28516914/adenylate-kinase-hcinap-determines-self-renewal-of-colorectal-cancer-stem-cells-by-facilitating-ldha-phosphorylation
#17
Yapeng Ji, Chuanzhen Yang, Zefang Tang, Yongfeng Yang, Yonglu Tian, Hongwei Yao, Xi Zhu, Zeming Zhang, Jiafu Ji, Xiaofeng Zheng
Targeting the specific metabolic phenotypes of colorectal cancer stem cells (CRCSCs) is an innovative therapeutic strategy for colorectal cancer (CRC) patients with poor prognosis and relapse. However, the context-dependent metabolic traits of CRCSCs remain poorly elucidated. Here we report that adenylate kinase hCINAP is overexpressed in CRC tissues. Depletion of hCINAP inhibits invasion, self-renewal, tumorigenesis and chemoresistance of CRCSCs with a loss of mesenchymal signature. Mechanistically, hCINAP binds to the C-terminal domain of LDHA, the key regulator of glycolysis, and depends on its adenylate kinase activity to promote LDHA phosphorylation at tyrosine 10, resulting in the hyperactive Warburg effect and the lower cellular ROS level and conferring metabolic advantage to CRCSC invasion...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28515423/mir-520b-as-a-novel-molecular-target-for-suppressing-stemness-phenotype-of-head-neck-cancer-by-inhibiting-cd44
#18
Ya-Ching Lu, Ann-Joy Cheng, Li-Yu Lee, Guo-Rung You, Yan-Liang Li, Hsin-Ying Chen, Joseph T Chang
Cancer stem cells preferentially acquire the specific characteristics of stress tolerance and high mobility, allowing them to progress to a therapy-refractive state. To identify a critical molecule to regulate cancer stemness is indispensable to erratically cure cancer. In this study, we identified miR-520b as a novel molecular target to suppress head-neck cancer (HNC) with stemness phenotype. MiR-520b inhibited cellular migration and invasion via the mechanism of epithelial-mesenchymal transition. It also sensitized cells to therapeutic drug and irradiation...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515364/nicotinamide-metabolism-regulates-glioblastoma-stem-cell-maintenance
#19
Jinkyu Jung, Leo J Y Kim, Xiuxing Wang, Qiulian Wu, Tanwarat Sanvoranart, Christopher G Hubert, Briana C Prager, Lisa C Wallace, Xun Jin, Stephen C Mack, Jeremy N Rich
Metabolic dysregulation promotes cancer growth through not only energy production, but also epigenetic reprogramming. Here, we report that a critical node in methyl donor metabolism, nicotinamide N-methyltransferase (NNMT), ranked among the most consistently overexpressed metabolism genes in glioblastoma relative to normal brain. NNMT was preferentially expressed by mesenchymal glioblastoma stem cells (GSCs). NNMT depletes S-adenosyl methionine (SAM), a methyl donor generated from methionine. GSCs contained lower levels of methionine, SAM, and nicotinamide, but they contained higher levels of oxidized nicotinamide adenine dinucleotide (NAD+) than differentiated tumor cells...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28514506/human-adipose-derived-mesenchymal-stem-cell-secreted-cxcl1-and-cxcl8-facilitate-breast-tumor-growth-by-promoting-angiogenesis
#20
Yuan Wang, Junli Liu, Qingyuan Jiang, Jie Deng, Fen Xu, Xiaolei Chen, Fuyi Cheng, Yujing Zhang, Yunqi Yao, Zhemin Xia, Xia Xu, Xiaolan Su, Meijuan Huang, Lei Dai, Yang Yang, Shuang Zhang, Dechao Yu, Robert Chunhua Zhao, Yuquan Wei, Hongxin Deng
Autologous adipose tissue or adipose tissue with additive adipose-derived mesenchymal stem cells (ADSCs) is used in the breast reconstruction of breast cancer patients who undergo mastectomy. ADSCs play an important role in the angiogenesis and adipogenesis, which make it much better than other materials. However, ADSCs may promote residual tumor cells to proliferate or metastasize, and the mechanism is still not fully understood. In our present study, we demonstrated that hADSCs could facilitate tumor cells growth after co-injection with MCF7 and ZR-75-30 breast cancer cells (BCCs) by promoting angiogenesis, but hADSCs showed limited effect on the growth of MDA-MB-231 BCCs...
May 17, 2017: Stem Cells
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