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Mingdi Zhang, Wei Gong, Bin Zuo, Bingfeng Chu, Zhaohui Tang, Yong Zhang, Yong Yang, Di Zhou, Mingzhe Weng, Yiyu Qin, Mingzhe Ma, Alex Jiang, Fei Ma, Zhiwei Quan
Cytokine is a key molecular link between chronic inflammation and gallbladder cancer (GBC) progression. The potential mechanism of cytokine-associated modulation of microRNAs (miRNAs) expression in GBC progression is not fully understood. In this study, we investigated the biological effects and prognostic significance of interleukin-6 (IL-6) -induced miRNAs in the development of GBC. We identify that inflammatory cytokine, IL-6 promotes proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of GBC both in vitro and in vivo...
October 15, 2016: Oncotarget
Xiaoyun Dai, Kwang Seok Ahn, Ling Zhi Wang, Chulwon Kim, Amudha Deivasigamni, Frank Arfuso, Jae-Young Um, Alan Prem Kumar, Young-Chae Chang, Dhiraj Kumar, Gopal C Kundu, Junji Magae, Boon Cher Goh, Kam Man Hui, Gautam Sethi
Increasing evidence(s) have indicated that epithelial to mesenchymal transition (EMT) at the advanced stage of liver cancer, not only has the ability to self-renew and progress cancer, but also enables greater resistance to conventional chemo- and radio-therapies. Here, we report that ascochlorin (ASC), an isoprenoid antibiotic could potentiate the cytotoxic effect of doxorubicin (DOX) on HCCLM3, SNU387, SNU49, and SK-Hep-1 hepatocellular carcinoma (HCC) cells, which had a predominantly mesenchymal signature with low expression of E-cadherin but high expression of N-cadherin...
October 7, 2016: Molecular Cancer Therapeutics
Lori E Lowes, David Goodale, Ying Xia, Carl Postenka, Matthew M Piaseczny, Freeman Paczkowski, Alison L Allan
Metastasis is the cause of most prostate cancer (PCa) deaths and has been associated with circulating tumor cells (CTCs). The presence of ≥5 CTCs/7.5mL of blood is a poor prognosis indicator in metastatic PCa when assessed by the CellSearch® system, the "gold standard" clinical platform. However, ~35% of metastatic PCa patients assessed by CellSearch® have undetectable CTCs. We hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and subsequent loss of necessary CTC detection markers, with important implications for PCa metastasis...
October 15, 2016: Oncotarget
Tao Yin, Guoping Wang, Sisi He, Guobo Shen, Chao Su, Yan Zhang, Xiawei Wei, Tinghong Ye, Ling Li, Shengyong Yang, Dan Li, Fuchun Guo, Zemin Mo, Yang Wan, Ping Ai, Xiaojuan Zhou, Yantong Liu, Yongsheng Wang, Yuquan Wei
Malignant pleural effusion (PE) and ascites, common clinical manifestations in advanced cancer patients, are associated with poor prognosis. However, the biological characteristics of malignant PE and ascites are not clarified. Here, we report that malignant PE and ascites can induce frequent epithelial-mesenchymal transition (EMT) program and endow tumor cells with stem cell properties with high efficiency, which promote tumor growth, chemoresistance and immune evasion. We determine that this EMT process is mainly dependent on VEGF, one initiator of PI3K/Akt/mTOR pathway...
October 18, 2016: Journal of Biological Chemistry
Xiaoxiao Lu, Honglan Guo, Xi Chen, Jian Xiao, Yong Zou, Wei Wang, Qiong Chen
According to recent research, Ras homolog gene family member C (RhoC) is confirmed to have a powerful regulatory effect on cell motility mediated by the cytoskeleton, and this process is closely associated with tumor invasion and metastasis. In addition, the epithelial-mesenchymal transition (EMT) process which causes cytoskeleton rearrangement, also plays a pivotal role in tumor invasion and metastasis.Consequently, in the present study, we aimed to ascertain whether RhoC has an effect on the EMT process induced by TGF-β1 in lung adenocarcinoma cells and whether RhoC promotes tumor invasion by mediating the occurrence of EMT...
October 4, 2016: Oncology Reports
Bhumika Wadhwa, Rashmi Dumbre
Prostate (CaP) cancer is the second-leading cause of cancer-related mortality in men in Western societies. Androgen receptor (AR) signaling is a critical survival pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the principal treatment for patients with locally advanced and metastatic disease. Although a majority of patients initially respond to ADT, most will eventually develop castrate resistance. The recent discovery that AR signaling persists during systemic castration via intratumoral production of androgens led to the development of novel anti-androgen therapies...
October 6, 2016: Chemico-biological Interactions
Zhongwei Li, Pingfu Hou, Dongmei Fan, Meichen Dong, Musong Ma, Hongyuan Li, Ruosi Yao, Yuxin Li, Guannan Wang, Pengyu Geng, Adhanom Mihretab, Dongxu Liu, Yu Zhang, Baiqu Huang, Jun Lu
EZH2 (the Enhancer of Zeste Homolog 2), as a key epigenetic regulator and EMT inducer, participates in a variety of cancer metastasis. EZH2 stability is regulated by several types of post-translational modifications (PTMs).The long non-coding RNAs (lncRNA) have been implicated to have critical roles in multiple carcinogenesis through a wide range of mechanisms, including modulating the stability of proteins. To date, whether the stability of EZH2 protein is regulated by lncRNAs remains unexplored. Here we report the discovery of ANCR modulating the stability of EZH2, and hence in the invasion and metastasis of breast cancer cells...
October 7, 2016: Cell Death and Differentiation
Jing Zhang, Xiao-Yu Chen, Ke-Jian Huang, Wei-Dong Wu, Tao Jiang, Jun Cao, Li-Sheng Zhou, Zheng-Jun Qiu, Chen Huang
The aim of the present study was to investigate the expression of forkhead box M1 (FoxM1) and E-cadherin in tissues of gastric cancer in order to reveal any correlation between FoxM1, E-cadherin and clinicopathological parameters. The association between FoxM1 and E-cadherin in the development and progression of gastric cancer was also investigated. The expression of FoxM1 and E-cadherin in gastric cancer and adjacent normal tissue on tissue microarray was detected using immunohistochemistry. The clinicopathological significance of FoxM1 and E-cadherin in gastric cancer was explored, and the association between FoxM1 and E-cadherin was further examined using statistical techniques...
October 2016: Oncology Letters
Natalija Filipovic, Katarina Vukojevic, Ivana Bocina, Marijan Saraga, Merica Glavina Durdov, Boris Kablar, Mirna Saraga-Babic
Differentiation of human podocytes starts with mesenchymal-to-epithelial transition (MET) of the metanephric mesenchyme into the S-shaped nephrons. During further development, differentiating podocytes regain mesenchyme-like cell characteristics by epithelial-to-mesenchymal transition (EMT), leading to formation of the terminally differentiated, non-dividing cell. Both MET and EMT processes involve changes in content and organization of cytoskeletal and actin filaments, accompanied by the increased glomerular vascularization...
October 1, 2016: Histochemistry and Cell Biology
D Wang, W Shi, Y Tang, Y Liu, K He, Y Hu, J Li, Y Yang, J Song
Prefoldin (PFDN) is a co-chaperone protein that is primarily known for its classic cytoplasmic functions in the folding of actin and tubulin monomers during cytoskeletal assembly. Here, we report a marked increase in prefoldin subunit 1 (PFDN1) levels during the transforming growth factor (TGF)-β1-mediated epithelial-mesenchymal transition (EMT) and in human lung tumor tissues. Interestingly, the nuclear localization of PFDN1 was also detected. These observations suggest that PFDN1 may be essential for important novel functions...
October 3, 2016: Oncogene
Q Zhou, X Wang, Z Yu, X Wu, X Chen, J Li, Z Zhu, B Liu, L Su
Gastric cancer (GC) is one of the most common types of cancer worldwide, and it involves extensive local tumour invasion, metastasis and poor prognosis. Understanding the mechanisms regulating the progression of GC is necessary for the development of effective therapeutic strategies. Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is an important regulator controlling gene activation and repression, which has been thought to be involved in tumorigenesis. However, the role of TBL1XR1 in human GC remains largely unknown...
October 3, 2016: Oncogene
D H Peng, C Ungewiss, P Tong, L A Byers, J Wang, J R Canales, P A Villalobos, N Uraoka, B Mino, C Behrens, I I Wistuba, R I Han, C A Wanna, M Fahrenholtz, K J Grande-Allen, C J Creighton, D L Gibbons
Lung cancer is the leading cause of cancer-related deaths, primarily due to distant metastatic disease. Metastatic lung cancer cells can undergo an epithelial-to-mesenchymal transition (EMT) regulated by various transcription factors, including a double-negative feedback loop between the microRNA-200 (miR-200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT promotes malignancy remain largely undefined. Although the cell-intrinsic effects of EMT are important for tumor progression, the reciprocal dynamic crosstalk between mesenchymal cancer cells and the extracellular matrix (ECM) is equally critical in regulating invasion and metastasis...
October 3, 2016: Oncogene
Li-Li Huang, Xiao-Lin Zhu, Wei-Qian Deng, Na Duan, Xiu-Jie Liang, Yue Wang, Ting-Ting Guo, Shuang-Shuang Shu, Xiao-Hong Xiang, Ting-Ting Jiang, Xun Tang, Jun Zhang
OBJECTIVE: To investigate whether the p38 mitogen-activated protein kinase (MAPK) signaling pathway mediates advanced oxidation protein products (AOPPs)-induced epithelial-to-mesenchymal transition (EMT) in tubular cells. METHODS: Human proximal tubular cells (HK-2 cells) exposed to AOPP-bovine serum albumin (BSA) were examined for expressions of p38 MAPK and phosphorylated p38 MAPK using Western blotting. Western blotting and quantitative RT-PCR were used to examine the protein and mRNA expressions of EMT markers E-cadherin and vimentin and endoplasmic reticulum stress marker glucose-regulated protein (GRP) 78 in cells treated with SB203580 (an inhibitor of the p38 MAPK signaling pathway) prior to AOPP exposure...
August 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Sung Un Kang, Jae Won Choi, Jae Won Chang, Kang Il Kim, Yeon Soo Kim, Ju Kyeong Park, Yang Eun Kim, Yun Sang Lee, Sang Sik Yang, Chul-Ho Kim
Advances in physics and biology have made it possible to apply non-thermal atmospheric pressure plasma (NTP) in the biomedical field. Although accumulating evidence suggests that NTP has various medicinal effects, such as facilitating skin wound healing on exposed tissue while minimizing undesirable tissue damage, the underlying molecular mechanisms are not fully understood. In this study, NTP generated from N2 optimized wound healing in the scratch wound healing assay. In addition, matrix metalloproteinase (MMP)-9 expression and enzyme activity increased and the urokinase-type plasminogen activator (uPA) system was activated after NTP treatment...
September 27, 2016: Experimental Dermatology
T Kwak, K Drews-Elger, A Ergonul, P C Miller, A Braley, G H Hwang, D Zhao, A Besser, Y Yamamoto, H Yamamoto, D El-Ashry, J M Slingerland, M E Lippman, B I Hudson
The receptor for advanced glycation end products (RAGE) is highly expressed in various cancers and is correlated with poorer outcome in breast and other cancers. Here we tested the role of targeting RAGE by multiple approaches in the tumor and tumor microenvironment, to inhibit the metastatic process. We first tested how RAGE impacts tumor cell-intrinsic mechanisms using either RAGE overexpression or knockdown with short hairpin RNAs (shRNAs). RAGE ectopic overexpression in breast cancer cells increased MEK-EMT (MEK-epithelial-to-mesenchymal transition) signaling, transwell invasion and soft agar colony formation, and in vivo promoted lung metastasis independent of tumor growth...
September 26, 2016: Oncogene
Wan-Hu Fan, Fen-Jing Du, Xiao-Jing Liu, Na Chen
Hypoxia-induced epithelial-to-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) was investigated. Frequently rearranged in advanced T-cell lymphomas-1 (FRAT1) is a positive regulator of the Wnt/β-catenin signaling pathway and is overexpressed in many human tumors. However, the expression and role of FRAT1 in HCC has not been elucidated. In this study, we investigated the effect of FRAT1 on EMT process in HCC cells induced by hypoxia. Our results showed that FRAT1 is highly expressed in HCC tissues and cell lines...
September 23, 2016: Oncology Reports
Hai-Xiang Gao, Li Yan, Chunzhi Li, Lian-Mei Zhao, Wei Liu
Crizotinib is an orally administered drug for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non‑small cell lung cancer (NSCLC). Despite the impressive efficacy of crizotinib in the treatment of ALK‑positive lung cancer, acquired resistance eventually develops in the majority of patients. The microRNA (miR)‑200c reverses the resistance of lung cancer cells to various chemotherapeutic drugs and molecular targeted drugs, however, whether it can reverse the resistance of crizotinib remains unknown...
September 23, 2016: Molecular Medicine Reports
C-C Liu, D-L Cai, F Sun, Z-H Wu, B Yue, S-L Zhao, X-S Wu, M Zhang, X-W Zhu, Z-H Peng, D-W Yan
We previously demonstrated that fermitin family member 1 (FERMT1) was significantly overexpressed in colon cancer (CC) and associated with poor metastasis-free survival. This study aimed to investigate the precise role of FERMT1 in CC metastasis and the mechanism by which FERMT1 is involved in the epithelial-mesenchymal transition (EMT). Correlations between FERMT1 and EMT markers (E-cadherin, Slug, N-cadherin and β-catenin) were examined via immunohistochemistry in a cohort of CC tissues and adjacent normal colon mucosae...
September 19, 2016: Oncogene
Priscila Guimarães de Marcondes, José Andrés Morgado-Díaz
Radiotherapy is widely used for advanced rectal tumors. However, refractory metastasis has become the major cause of therapy failure in rectal cancer patients. Understanding the molecular mechanism that controls the aggressive cellular response to this treatment is essential for developing new therapeutic applications and improving radiotherapy response in colorectal cancer patients. Using the progeny of cells that were submitted to irradiation, we have demonstrated that the PI3K/AKT, Wnt/β-catenin signaling pathways as well as ERK1/2 downstream of EPHA4 receptor activation, play an important role in the regulation of events related with the EMT development, which may be associated with the therapeutic failure in rectal cancer after radiotherapy...
September 15, 2016: Journal of Cellular Biochemistry
D Fang, H Chen, J Y Zhu, W Wang, Y Teng, H-F Ding, Q Jing, S-B Su, S Huang
Epithelial-mesenchymal transition (EMT) is regarded as a crucial contributing factor to cancer progression. Diverse factors have been identified as potent EMT inducers in ovarian cancer. However, molecular mechanism sustaining EMT of ovarian cancer cells remains elusive. Here we show that the presence of SOS1/EPS8/ABI1 complex is critical for sustained EMT traits of ovarian cancer cells. Consistent with the role of SOS1/EPS8/ABI1 complex as a Rac1-specific guanine nucleotide exchange factor, depleting Rac1 results in the loss of most of mesenchymal traits in mesenchymal-like ovarian cancer cells, whereas expressing constitutively active Rac1 leads to EMT in epithelial-like ovarian cancer cells...
September 12, 2016: Oncogene
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