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Yujuan Zhou, Qianjin Liao, Yaqian Han, Jie Chen, Zhigang Liu, Hang Ling, Jing Zhang, Wenjuan Yang, Linda Oyang, Longzheng Xia, Li Wang, Heran Wang, Lei Xue, Hui Wang, Bingqiang Hu
Objective: Ras-related C3 botulinum toxin substrate1(Rac1) and epithelial mesenchymal transition (EMT) are key therapeutic targets in cancer. We investigated the clinical significance of Rac1 and markers of EMT expression in non-small cell lung cancer (NSCLC), and their possible correlation with EMT phenotype. Methods: Immunohistochemistry was used to assess the expression of Rac1, Snail1, Twist1, N-cadherin (N-cad), Vimentin (Vim), and E-cadherin (E-cad) in 153 NSCLC paraffin-embedded specimens and 45 normal specimens adjacent to tumors...
2016: Journal of Cancer
Zongji Zheng, Meiping Guan, Yijie Jia, Dan Wang, Ruoyu Pang, Fuping Lv, Zhizhou Xiao, Ling Wang, Hongbin Zhang, Yaoming Xue
MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy. Here, we compared the protective efficacies of miR-26a and miR-30c in renal tubular epithelial cells (NRK-52E) and determined whether they demonstrated additive effects in the attenuation of renal fibrosis. TGFβ1 suppressed miR-26a and miR-30c expression but up-regulated pro-fibrotic markers in NRK-52E cells, and these changes were also found in the kidney cortex of 40-week-old diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats...
November 22, 2016: Scientific Reports
Chengxin Sun, Lin Jiang, Yan Liu, Hong Shen, Stephen J Weiss, Yifa Zhou, Liangyou Rui
Lipolysis provides metabolic fuel; however, aberrant adipose lipolysis results in ectopic lipid accumulation and lipotoxicity. While adipose triacylglycerol lipase (ATGL) catalyzes the first step of lipolysis, its regulation is not fully understood. Here, we demonstrate that adipocyte Snail1 suppresses both ATGL expression and lipolysis. Adipose Snail1 levels are higher in fed mice than in fasted mice and higher in obese mice as opposed to lean mice. Insulin increases Snail1 levels in both murine and human adipocytes, wherein Snail1 binds to the ATGL promoter to repress its expression...
November 15, 2016: Cell Reports
Jei Ha Lee, Jung Yul Kim, Seo Yeon Kim, Soo Im Choi, Kuk Chan Kim, Eun Wie Cho, In Gyu Kim
Amyloid β precursor protein binding family B member 1(APBB1) was first identified as a binding partner of amyloid precursor protein during brain development, but its function in the context of cancer remain unclear. Here we show for the first time that APBB1 is partly associated with intensifying cancer stem cell(CSC) and epithelial-to-mesenchymal transition (EMT) and enhancing radiation-resistant properties of lung cancer cells. We found that APBB1 was highly expressed in ALDH1(high) CSC-like cells sorted from A549 lung cancer cells...
November 9, 2016: Biochemical and Biophysical Research Communications
Haiyu Wang, Yusheng Chen, Guohao Wu
Succinate dehydrogenase (SDH) is a heterotetrameric complex, among which the catalytic core SDHB loss-of-function mutations lead to mitochondrial enzyme SDH dysfunction and are associated with cancer formation. However, the impact of SDHB loss on colorectal carcinoma and the underlying mechanisms are largely unknown. In this study, we found a coherent decreased SDHB expression both in human colorectal cancer (CRC) samples and CRC cell lines. Combined clinical analysis in a cohort of 43 CRC patients demonstrated a correlation between reduced SDHB activity and a more advanced clinical phenotype regarding lymphatic and distant metastasis...
November 3, 2016: Translational Oncology
Y U Kamata, Tomoki Sumida, Yosuke Kobayashi, Akiko Ishikawa, Wataru Kumamaru, Yoshihide Mori
AIM: Inhibitor of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors that generally stimulate cell proliferation and inhibit differentiation. However, the role of ID2 in cancer progression remains ambiguous. Here, we investigated the function of ID2 in ID2-null oral squamous cell carcinoma (OSCC) cells. MATERIALS AND METHODS: We introduced an ID2 cDNA construct into ID2-null OSCC cells and compared them with empty-vector-transfected cells in terms of cell proliferation, invasion, and activity and expression of matrix metalloproteinase (MMP)...
November 2016: Cancer Genomics & Proteomics
Seung-Hyun Jeong, You-Jin Jeon, Sun Joo Park
Hypoxia-induced epithelial-mesenchymal transition (EMT) has been identified as essential for tumor progression and metastasis. The present study examined the effects of an antioxidant, dieckol, on hypoxia‑induced EMT in HT29 human colorectal cancer cells. HT29 cells were treated with a hypoxia‑inducing agent, CoCl2, and an increase in the levels of intracellular reactive oxygen species (ROS) and various morphological changes, such as loss of cell‑cell contact and aggressive cell migration were observed...
October 21, 2016: Molecular Medicine Reports
Denghe Liu, Lu Sun, Xue Qin, Tianhua Liu, Shu Zhang, Yinkun Liu, Shan Li, Kun Guo
OBJECTIVE: Reprogramming energy metabolism has been defined as the ninth hallmark of cancer; glucose deprivation might be a novel, feasible and effective approach for cancer treatment. However, the comprehensive illustration of behavior alteration of hepatocellular carcinoma (HCC) cells induced by glucose restriction is lacking and associated molecular mechanism is still unclear. METHODS: Three human HCC cell lines were cultured with normal control (25.0 mM D-glucose) and low glucose (5...
September 2016: Discovery Medicine
Ting Ni, Xiao-Yan Li, Na Lu, Teng An, Zhi-Ping Liu, Rong Fu, Wen-Cong Lv, Yi-Wei Zhang, Xiao-Jun Xu, R Grant Rowe, Yong-Shun Lin, Amanda Scherer, Tamar Feinberg, Xiao-Qi Zheng, Bao-An Chen, X Shirley Liu, Qing-Long Guo, Zhao-Qiu Wu, Stephen J Weiss
The zinc-finger transcription factor Snail1 is inappropriately expressed in breast cancer and associated with poor prognosis. While interrogating human databases, we uncovered marked decreases in relapse-free survival of breast cancer patients expressing high Snail1 levels in tandem with wild-type, but not mutant, p53. Using a Snail1 conditional knockout model of mouse breast cancer that maintains wild-type p53, we find that Snail1 plays an essential role in tumour progression by controlling the expansion and activity of tumour-initiating cells in preneoplastic glands and established tumours, whereas it is not required for normal mammary development...
October 17, 2016: Nature Cell Biology
Jing Zuo, Dahu Wang, Haitao Shen, Fengling Liu, Jing Han, Xianghong Zhang
One of the important mediators of Epithelial to mesenchymal transition (EMT) is the Snail1 protein (encoded by SNAI1) which facilitates transition to mesenchymal state by transcriptionally repressing the epithelial cell marker E-cadherin. Given its central role in EMT and tumor metastasis, the cell has evolved multiple levels of regulatory mechanism at transcriptional, post-transcriptional, and post-translational level to regulate SNAI1 expression. Recently, miR-153 has been shown to regulate SNAI1 expression in hepatocellular carcinoma...
October 13, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Hirak Biswas, Gregory D Longmore
Hypoxic injury to the heart results in cardiac fibrosis that leads to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor implicated in fibrosis following organ injury and cancer. To determine if the action of SNAIL1 contributed to cardiac fibrosis following hypoxic injury, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 expression is upregulated in the infarcted heart, especially in the myofibroblasts. Utilizing primary cardiac fibroblasts in ex vivo cultures we find that pro-fibrotic factors and collagen I increase SNAIL1 protein level...
2016: PloS One
Baohui Liu, Huimin Dong, Xi Lin, Xiangsheng Yang, Xiaojing Yue, Jian Yang, Yuntao Li, Liquan Wu, Xiaonan Zhu, Shenqi Zhang, Daofeng Tian, Junmin Wang, Qiang Cai, Shanping Mao, Qianxue Chen, Jiang Chang
Activation of Snail1 signaling promotes the migration and invasion of multiple tumors, including glioblastoma multiforme (GBM). However, the molecular mechanism that augments Snail1 signaling during GBM cell migration and invasion remains largely unknown. Identification of the factors that regulate Snail1 signaling is critical to block tumor cell migration and invasion. By screening human GBM specimens, we found that the expression levels of small GTPase RND3 positively correlated with the expression levels of E-cadherin and claudin, the glioblastoma migration biomarkers negatively regulated by Snail1...
October 1, 2016: Oncotarget
Xiaocheng Cao, Hui Zou, Jianguo Cao, Yinghong Cui, Shuwen Sun, Kaiqun Ren, Zhenwei Song, Duo Li, Meifang Quan
BACKGROUND: Cancer stem cells (CSCs) are considered as the origin of tumor relapse. Here, we investigated the effects of Fructus Viticis total flavonoids (FVTF) on the characteristics of lung cancer stem-like cells (LCSLCs) derived from human small cell lung cancer NCI-H446 cell line and its potential mechanism. METHODS: Human small cell lung cancer NCI-H446 cell line was cultured in vitro. The CD133(+) cells were sorted from NCI-H446 cell line by magnetic separation...
2016: BMC Complementary and Alternative Medicine
Zhiyun Xu, Encheng Li, Zhe Guo, Ruofei Yu, Hualong Hao, Yitong Xu, Zhao Sun, Xiancheng Li, Jianxin Lyu, Qi Wang
Metastasis is a complex pathophysiological process. As the main cause of cancer mortality in humans it represents a serious challenge to both basic researchers and clinicians. Here we report the design and construction of a multi-organ microfluidic chip that closely mimics the in vivo microenvironment of lung cancer metastasis. This multi-organs-on-a-chip includes an upstream "lung" and three downstream "distant organs", with three polydimethylsiloxane (PDMS) layers and two thin PDMS microporous membranes bonded to form three parallel microchannels...
October 5, 2016: ACS Applied Materials & Interfaces
John R Montford, Allison M B Lehman, Micah S Scobey, Mary C M Weiser-Evans, Raphael A Nemenoff, Seth B Furgeson
The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme controls the release of arachidonic acid from membrane bound phospholipids and is the rate-limiting step in production of eicosanoids. A variety of different kidney injuries activate cPLA2α, therefore we hypothesized that cPLA2α activity would regulate pathologic processes in HK-2 cells, a human renal tubular epithelial cell line, by regulating cell phenotype and proliferation. In two lentiviral cPLA2α-silenced knockdowns, we observed decreased proliferation and increased apoptosis compared to control HK-2 cells...
November 2016: Prostaglandins & Other Lipid Mediators
Haruki Arévalo-Romero, Isaura Meza, Gabriela Vallejo-Flores, Ezequiel M Fuentes-Pananá
Gastric cancer is the third cause of cancer death worldwide and infection by Helicobacter pylori (H. pylori) is considered the most important risk factor, mainly by the activity of its virulence factor CagA. H. pylori/CagA-induced chronic inflammation triggers a series of gastric lesions of increased severity, starting with gastritis and ending with cancer. IL-1β has been associated with tumor development and invasiveness in different types of cancer, including gastric cancer. Currently, it is not clear if there is an association between CagA and IL-1β at a cellular level...
2016: Gastroenterology Research and Practice
Oskar Schnappauf, Sven Beyes, Annika Dertmann, Vivien Freihen, Patrick Frey, Sabine Jägle, Katja Rose, Tom Michoel, Rudolf Grosschedl, Andreas Hecht
Transcriptional silencing is a major cause for the inactivation of tumor suppressor genes, however, the underlying mechanisms are only poorly understood. The EPHB2 gene encodes a receptor tyrosine kinase that controls epithelial cell migration and allocation in intestinal crypts. Through its ability to restrict cell spreading, EPHB2 functions as a tumor suppressor in colorectal cancer whose expression is frequently lost as tumors progress to the carcinoma stage. Previously we reported that EPHB2 expression depends on a transcriptional enhancer whose activity is diminished in EPHB2 non-expressing cells...
November 2016: Biochimica et Biophysica Acta
Lorena Alba-Castellón, Ruben Olivera-Salguero, Aida Mestre-Farrera, Raul Pena, Mercedes Herrera, Felix Bonilla, J Ignacio Casal, Josep Baulida, Cristina Pena, Antonio Garcia de Herreros
Snail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here an EMT-independent action of Snail1 on tumor invasion since it is required for the activation of cancer-associated fibroblasts (CAFs). Snail1 expression in fibroblast requires signals derived from tumor cells such as TGF-beta; reciprocally, in fibroblasts Snail1 organizes a complex program that stimulates invasion of epithelial cells independent on the expression of Snail1 in these cells...
August 8, 2016: Cancer Research
Ying Wu, Hui Lyu, Hongbing Liu, Xuefei Shi, Yong Song, Bolin Liu
Long noncoding RNA (lncRNA) plays pivotal roles in cancer development. To date, only a small number of lncRNAs have been characterized at functional level. Here, we discovered a novel lncRNA termed GAS5-AS1 as a tumor suppressor in non-small cell lung cancer (NSCLC). The expression of GAS5-AS1 in NSCLC tumors was much lower than that in the adjacent normal lung tissues. The reduced GAS5-AS1 was significantly correlated with larger tumors, higher TNM stages, and lymph node metastasis in NSCLC patients. While ectopic expression or specific knockdown of GAS5-AS1 had no effect on proliferation, cell cycle progression, and apoptosis, it dramatically decreased or increased, respectively, NSCLC cell migration and invasion...
2016: Scientific Reports
Hayriye Sayarlioglu, Ali Okuyucu, Abdulkerim Bedir, Osman Salis, Eser Yenen, Garip Bekfilavioglu, Coskun Kaya
AIM: Contrast medium-induced nephropathy is one of the major complications of intravenous contrast medium use. But its pathogenesis is unclear. Epithelial mesenchymal transition (EMT) is defined as the transformation of the primer epithelial cells to mesenchymal cells. EMT in tubular cells might cause tubulointerstitial damage. In this study, we investigated whether or not EMT has a role in radiocontrast-induced nephropathy. Radiocontrast medium might be triggering reversible EMT via serum and glucocorticoid-regulated kinase 1 (SGK 1)...
September 2016: Renal Failure
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