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epithelial to mesenchymal transition

Giorgio Ivan Russo, Simone Bier, Jörg Hennenlotter, Gunthild Beger, Lucretia Pavlenco, Jens van de Flierdt, Siegfried Hauch, Moritz Maas, Simon Walz, Steffen Rausch, Jens Bedke, Giuseppe Morgia, Arnulf Stenzl, Tilman Todenhöfer
OBJECTIVE: To evaluate the presence of circulating tumour cells (CTC) at different stages of prostate cancer (PC) using the ProstateCancerDetect kit. Moreover, we aimed to assess the expression of transcripts that are specific for cancer stem cells (AdnaTest StemCell) and epithelial mesenchymal transition (EMT) in CTC (AdnaTest EMT) as well as additional genes that are known to promote PC progression. PATIENTS AND METHODS: In this prospective study, we included 81 patients who underwent treatment for PC between 07/2014 and 02/2015, including A) 18 patients (22...
March 15, 2018: BJU International
Weinan Guo, Jinyuan Ma, Tianli Pei, Tao Zhao, Sen Guo, Xiuli Yi, Yu Liu, Shiyu Wang, Guannan Zhu, Zhe Jian, Tianwen Gao, Chunying Li, Wenjun Liao, Qiong Shi
Melanoma is the most malignant skin cancer with increasing incidence worldwide. Although innovative therapies such as BRAF inhibitor and immune checkpoint inhibitor have gained remarkable advances, metastatic melanoma remains an incurable disease for its notorious aggressiveness. Therefore, further clarification of the underlying mechanism of melanoma pathogenesis is critical for the improvement of melanoma therapy. Ubiquitination is an important regulatory event for cancer hallmarks and melanoma development, and the deubiquitinating enzymes including ubiquitin-specific peptidase (USP) families are greatly implicated in modulating cancer biology...
March 14, 2018: Journal of Cellular and Molecular Medicine
Muhammad Ramzan Manwar Hussain, Zeeshan Iqbal, Wajahat M Qazi, Daniel C Hoessli
The structural and functional diversity of the human proteome is mediated by N - and O- linked glycosylations that define the individual properties of extracellular and membrane-associated proteins. In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N -glycosylation. Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the N -glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins...
2018: Frontiers in Oncology
Fernando Revert, Francisco Revert-Ros, Raül Blasco, Aida Artigot, Ernesto López-Pascual, Roberto Gozalbo-Rovira, Ignacio Ventura, Elain Gutiérrez-Carbonell, Nuria Roda, Daniel Ruíz-Sanchis, Jerónimo Forteza, Javier Alcácer, Alejandra Pérez-Sastre, Ana Díaz, Enrique Pérez-Payá, Juan F Sanz-Cervera, Juan Saus
Goodpasture antigen-binding protein (GPBP) is an exportable1 Ser/Thr kinase that induces collagen IV expansion and has been associated with chemoresistance following epithelial-to-mesenchymal transition (EMT). Here we demonstrate that cancer EMT phenotypes secrete GPBP (mesenchymal GPBP) which displays a predominant multimeric oligomerization and directs the formation of previously unrecognized mesh collagen IV networks (mesenchymal collagen IV). Yeast two-hybrid (YTH) system was used to identify a260 SHCIE264 motif critical for multimeric GPBP assembly which then facilitated design of a series of potential peptidomimetics...
February 16, 2018: Oncotarget
Xin Chen, Yufei Fu, Hongfei Xu, Peng Teng, Qiong Xie, Yiran Zhang, Caochong Yan, Yiqiao Xu, Chunqi Li, Jianying Zhou, Yiming Ni, Weidong Li
Lung cancer is the leading cause of cancer-related death worldwide. Epithelial-mesenchymal transition (EMT) promotes lung cancer progression and metastasis, especially in lung adenocarcinoma. Sex determining region Y-box protein 5 (SOX5) is known to stimulate the progression of various cancers. Here, we used immunohistochemical analysis to reveal that SOX5 levels were increased in 90 lung adenocarcinoma patients. The high SOX5 expression in lung adenocarcinoma and non-tumor counterparts correlated with the patients' poor prognosis...
February 16, 2018: Oncotarget
Sebastian Buschauer, Andreas Koch, Philipp Wiggermann, Martina Müller, Claus Hellerbrand
Transarterial chemoembolization (TACE) is an established therapeutic approach for the treatment of hepatocellular carcinoma (HCC). Although patients who undergo TACE may have prolonged survival, there are indications that the malignancy of residual HCC tissue can increase subsequent to the procedure. Although hypoxia, which occurs during TACE due to ischemia, is known to contribute to angiogenesis, little is known with regard to the undesirable effects of chemotherapeutic agents on residual HCC cells. Doxorubicin is one of the most commonly used drugs in TACE...
April 2018: Oncology Letters
Jing Zhang, Yinghong Cui, Shuwen Sun, Jianguo Cao, Xiaoling Fang
Casticin inhibits migration, invasion and induced apoptosis in numerous cancer cells; however, the Hedgehog (Hh) signaling pathway is a key factor in the epithelial-mesenchymal transition (EMT). The present study aimed to assess whether casticin affects the expression of members of the Hh signaling pathway and EMT effectors in ovarian carcinoma. The ovarian cancer SKOV3 cell line was incubated in the presence of various concentrations of casticin or cyclopamine. Next, the expression levels of the main Hh signaling effector glioma-associated oncogene-1 (Gli-1) and EMT-associated factors [Twist-related protein 1 (Twist1), E-cadherin and N-cadherin] were determined by western blotting and reverse transcription-quantitative polymerase chain reaction...
April 2018: Oncology Letters
Tao Zhang, Guannan Zhao, Chuanhe Yang, Peixin Dong, Hidemichi Watari, Lin Zeng, Lawrence M Pfeffer, Junming Yue
Ovarian cancer is one of the most common malignancies in women and has a high mortality rate due to metastatic progression and tumor recurrence. ASAP1 (ArfGAP with SH3 Domain, Ankyrin Repeat and PH Domain 1) is an ADP-ribosylation factor GTPase-activating protein, which is involved in tumor metastasis. However, the role of ASAP1 in ovarian cancer is completely unknown. The present study reported that ASAP1 was highly expressed in ovarian carcinoma, and expression positively-correlated with overall poor survival and prognosis of patients...
April 2018: Oncology Letters
Shencun Fang, Huifang Guo, Yusi Cheng, Zewei Zhou, Wei Zhang, Bing Han, Wei Luo, Jing Wang, Weiping Xie, Jie Chao
Excessive proliferation and migration of fibroblasts contribute to pulmonary fibrosis in silicosis, and both epithelial cells and endothelial cells participate in the accumulation of fibroblasts via the epithelial-mesenchymal transition (EMT) and the endothelial-mesenchymal transition (EndMT), respectively. A mouse endothelial cell line (MML1) was exposed to silicon dioxide (SiO2 , 50 μg/cm2 ), and immunofluorescence and western blot analyses were performed to evaluate levels of specific endothelial and mesenchymal markers and to elucidate the mechanisms by which SiO2 induces the EndMT...
March 14, 2018: Cell Death & Disease
Hyeonseok Ko, Seongrak Kim, Kyungmi Yang, Kunhong Kim
Epithelial-mesenchymal transition (EMT) is a critical process in invasion and metastasis of cancer cells. E-cadherin to N-cadherin switching is considered a molecular hallmark of EMT. Recently, we reported that increased CK2 activity fully induces E-cadherin to N-cadherin switching, but the molecular mechanisms of N-cadherin upregulation are unknown. In this study, we examined how N-cadherin is upregulated by CK2. N-cadherin promoter analysis and ChIP analysis identified and confirmed myeloid zinc finger 1 (MZF1) as an N-cadherin transcription factor...
March 13, 2018: Oncogenesis
Belén Prados, Paula Gómez-Apiñániz, Tania Papoutsi, Guillermo Luxán, Stephane Zaffran, José María Pérez-Pomares, José Luis de la Pompa
During mammalian heart development, restricted myocardial Bmp2 expression is a key patterning signal for atrioventricular canal specification and the epithelial-mesenchyme transition that gives rise to the valves. Using a mouse transgenic line conditionally expressing Bmp2, we show that widespread Bmp2 expression in the myocardium leads to valve and chamber dysmorphogenesis and embryonic death by E15.5. Transgenic embryos show thickened valves, ventricular septal defect, enlarged trabeculae and dilated ventricles, with an endocardium able to undergo EMT both in vivo and in vitro...
March 14, 2018: Cell Death & Disease
Wen Ye, Shaoping Ling, Ran-Yi Liu, Zhi-Zhong Pan, Gaoyuan Wang, Shijuan Gao, Jiangxue Wu, Lihua Cao, Lili Dong, Yingchang Li, Yi Zhou, Wuying Du, Xiangqi Meng, Jinna Chen, Xinyuan Guan, Yulong He, Changchuan Pan, X F Steven Zheng, Xuemei Lu, Shuai Chen, Wenlin Huang
Colorectal cancer (CRC) is the third most common cancer worldwide, with more than 1.3 million new cases and 690,000 deaths each year. In China, the incidence of CRC has increased dramatically due to dietary and lifestyle changes, to become the fifth leading cause of cancer-related death. Here, we performed whole-exome sequencing in 50rectal cancer cases among the Chinese population as part of the International Cancer Genome Consortium research project. Frequently-mutated genes and enriched pathways were identified...
March 14, 2018: Journal of Pathology
Juliana Porretti, Guillermo N Dalton, Cintia Massillo, Georgina D Scalise, Paula L Farré, Randolph Elble, Esther N Gerez, Paula Accialini, Ana M Cabanillas, Kevin Gardner, Paola De Luca, Adriana De Siervi
Prostate cancer (PCa) is the most common cancer among men. Metabolic syndrome (MeS) is associated with increased PCa aggressiveness and recurrence. Previously, we proposed C-terminal binding protein 1 (CTBP1), a transcripcional co-repressor, as a molecular link between these two conditions. Notably, CTBP1 depletion decreased PCa growth in MeS mice. The aim of this study was to investigate the molecular mechanisms that explain the link between MeS and PCa mediated by CTBP1. We found that CTBP1 repressed Chloride Channel Accessory 2 (CLCA2) expression in prostate xenografts developed in MeS animals...
March 14, 2018: International Journal of Cancer. Journal International du Cancer
Wei Zhang, Luc Girard, Yu-An Zhang, Tomohiro Haruki, Mahboubeh Papari-Zareei, Victor Stastny, Hans K Ghayee, Karel Pacak, Trudy G Oliver, John D Minna, Adi F Gazdar
Background: Small cell lung cancer (SCLC) is a deadly, high grade neuroendocrine (NE) tumor without recognized morphologic heterogeneity. However, over 30 years ago we described a SCLC subtype with "variant" morphology which did not express some NE markers and exhibited more aggressive growth. Methods: To quantitate NE properties of SCLCs, we developed a 50-gene expression-based NE score that could be applied to human SCLC tumors and cell lines, and genetically engineered mouse (GEM) models...
February 2018: Translational Lung Cancer Research
Xuejiao Li, Zhongxiu Jiang, Xiangmin Li, Xiaoye Zhang
Osteopontin (OPN) is a promoter for tumor progression. It has been reported to promote non-small cell lung cancer (NSCLC) progression via the activation of nuclear factor-κB (NF-κB) signaling. As the increased acetylation of NF-κB p65 is linked to NF-κB activation, the regulation of NF-κB p65 acetylation could be a potential treatment target for OPN-induced NSCLC progression. Sirtuin 1 (SIRT1) is a deacetylase, and the role of SIRT1 in tumor progression is still controversial. The effect and mechanism of SIRT1 on OPN-induced tumor progression remains unknown...
2018: OncoTargets and Therapy
Jiaolong Shi, Fengping Li, Xingxing Yao, Tingyu Mou, Zhijun Xu, Zheng Han, Siyu Chen, Wende Li, Jiang Yu, Xiaolong Qi, Hao Liu, Guoxin Li
Trastuzumab is the only target to be approved as the first-line treatment of HER2 positive metastatic gastric cancer, but ubiquitous resistance decreases its therapeutic benefit. In this study, we found HER4, phosphorylation HER4 (p-HER4) and the mesenchymal marker Vimentin increased in trastuzumab-resistant cells (MKN45TR and NCI-N87TR), while epithelial markers expressions in trastuzumab-resistant cell lines and animal models decreased. Additionally, silencing HER4 prevented the epithelial-mesenchymal transition and led to decreased proliferation and migration in vitro and in vivo...
March 14, 2018: Oncogene
Motoki Takaku, Sara A Grimm, John D Roberts, Kaliopi Chrysovergis, Brian D Bennett, Page Myers, Lalith Perera, Charles J Tucker, Charles M Perou, Paul A Wade
GATA3 is frequently mutated in breast cancer; these mutations are widely presumed to be loss-of function despite a dearth of information regarding their effect on disease course or their mechanistic impact on the breast cancer transcriptional network. Here, we address molecular and clinical features associated with GATA3 mutations. A novel classification scheme defines distinct clinical features for patients bearing breast tumors with mutations in the second GATA3 zinc-finger (ZnFn2). An engineered ZnFn2 mutant cell line by CRISPR-Cas9 reveals that mutation of one allele of the GATA3 second zinc finger (ZnFn2) leads to loss of binding and decreased expression at a subset of genes, including Progesterone Receptor...
March 13, 2018: Nature Communications
Won Kyung Kim, Woong Sub Byun, Hwa-Jin Chung, Jedo Oh, Hyen Joo Park, Jae Sue Choi, Sang Kook Lee
Colorectal cancer (CRC) is the most common malignant disease worldwide due to its metastasis via the epithelial-mesenchymal transition (EMT) process. E-cadherin and Wnt signaling are emerging as potential targets for suppressing the EMT. In this context, Axin2 has been recognized as a negative regulator that inhibits glycogen synthase kinase 3β (GSK3β)-mediated degradation of Snail1, a transcriptional repressor of E-cadherin. However, Axin2 can also impede Wnt signaling via β-catenin degradation. Therefore, Axin2 may serve as either a promoter or suppressor of tumors, and the effects of its inhibition on the cell proliferation and metastasis of CRC require further elucidation...
March 10, 2018: Biochemical Pharmacology
Sheng Liu, Josephine Iaria, Richard J Simpson, Hong-Jian Zhu
BACKGROUND: Transformation by oncogene Ras overcomes TGF-β mediated growth inhibition in epithelial cells. However, it cooperates with each other to mediate epithelial to mesenchymal transition (EMT). The mechanism of how these two pathways interact with each other is controversial. METHODS: Molecular techniques were used to engineer expression plasmids for Ras, SPRY, TGF-β receptors, type I and II and ubiquitin. Immunoprecipitation and western blots were employed to determine protein-protein interactions, preotein levels, protein phosphorylation while immunofluorecesent staining for molecular co-localization...
March 13, 2018: Cell Communication and Signaling: CCS
C X Zhu, W Z Li, Y L Guo, L Chen, G H Li, J J Yu, B Shu, S Peng
Raf kinase inhibitory protein (RKIP) is a well-established metastasis suppressor that is frequently down-regulated in aggressive cancers. However, the impact of RKIP on cancer cell invasion and metastasis in prostate cancer is still elusive. To this end, we overexpressed RKIP in two prostate cancer cell lines. We found that overexpression of RKIP inhibited prostate cancer cells proliferation, migration and invasion. Mechanistically, we found that RKIP overexpression led to down-regula- tion of the NF-kB signaling pathway and inhibition of the epithelial-to-mesenchymal transition, which is important step for cancer metastasis...
2018: Neoplasma
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