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Ali Ben Djoudi Ouadda, Yi He, Viviane Calabrese, Hidetaka Ishii, Rony Chidiac, Jean-Philippe Gratton, Philippe P Roux, Nathalie Lamarche-Vane
Cdc42 GTPase-activating protein (CdGAP, also named ARHGAP31) is a negative regulator of the GTPases Rac1 and Cdc42. Associated with the rare developmental disorder Adams-Oliver Syndrome (AOS), CdGAP is critical for embryonic vascular development and VEGF-mediated angiogenesis. Moreover, CdGAP is an essential component in the synergistic interaction between TGFβ and ErbB-2 signaling pathways during breast cancer cell migration and invasion, and is a novel E-cadherin transcriptional co-repressor with Zeb2 in breast cancer...
February 20, 2018: Oncotarget
Jinghua Liu, Zhen Yu, Yuanyuan Xiao, Qiong Meng, Yeying Wang, Wei Chang
Background: The Forkhead transcription family member FOXA2 plays a fundamental role in hepatocellular carcinoma (HCC) progression, but the precise interaction factor and molecular regulation of FOXA2 are not fully understood. Objective: In this study, we found that FOXA2 could interact with sirtuin 6 (SIRT6) directly in vivo and in vitro. We explored that the expressions of FOXA2 and SIRT6 were significantly downregulated in human HCC and HCC cell lines. Methods: Functionally, cell counting kit-8 assay and Transwell® assay were performed; we demonstrated that the knockdown of FOXA2 and SIRT6 promoted HepG2 cells and Huh7 cells proliferation and invasion in vitro...
2018: Cancer Management and Research
Jun Won Park, Min-Sik Kim, Dominic C Voon, Su-Jin Kim, Jingi Bae, Dong-Gi Mun, Seung-Ik Ko, Hark Kyun Kim, Sang-Won Lee, Dae-Yong Kim
The molecular mechanisms underlying the pathogenesis of diffuse-type gastric cancer (DGC) have not been adequately explored due to a scarcity of appropriate animal models. A recently developed tool well suited for this line of investigation is the Pdx-1-Cre;Cdh1F/+ ;Trp53F/F ;Smad4F/F (pChe PS) mouse model that spontaneously develops metastatic DGC showing nearly complete E-cadherin loss. Here, we performed a proteogenomic analysis to uncover the molecular changes induced by the concurrent targeting of E-cadherin, p53, and Smad4 loss...
March 12, 2018: Molecular Carcinogenesis
Cong Ye, Yubo Hu, Junrong Wang
A large number of microRNAs (miRNAs) are aberrantly expressed in cervical cancer and play crucial roles in the onset and progression of cervical cancer by acting as either oncogene or tumor suppressor. Therefore, investigation on the expression, biological roles and underlying mechanisms of miRNAs in cervical cancer might provide valuable therapeutic targets in the treatment for patients with this disease. In this study, miRNA377 (miR-377) was downregulated in cervical cancer tissues and cell lines. Decreased miR-377 expression was strongly correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis and distant metastasis in patients with cervical cancer...
March 9, 2018: Oncology Research
Yu Okamoto, Naoko Nishimura, Kazunari Matsuda, Deshani C Ranawakage, Yusuke Kamachi, Hisato Kondoh, Masanori Uchikawa
To elucidate the transcriptional regulation that underlies specification of the otic placode, we investigated the Sox3 downstream enhancer Otic1 of the chicken, the activity of which is restricted to and distributed across the entire otic placode. The 181-bp Otic1 enhancer sequence was dissected into a 68-bp minimal activating sequence, which exhibited dimer enhancer activity in the otic placode and cephalic neural crest, and this was further reduced to a 25-bp Otic1 core sequence, which also showed octamer enhancer activity in the same regions...
March 8, 2018: Development, Growth & Differentiation
Pelin Balcik-Ercin, Metin Cetin, Irem Yalim-Camci, Gorkem Odabas, Nurettin Tokay, A Emre Sayan, Tamer Yagci
BACKGROUND: ZEB2 is a transcriptional repressor that regulates epithelial-to-mesenchymal transition (EMT) through binding to bipartite E-box motifs in gene regulatory regions. Despite the abundant presence of E-boxes within the human genome and the multiplicity of pathophysiological processes regulated during ZEB2-induced EMT, only a small fraction of ZEB2 targets has been identified so far. Hence, we explored genome-wide ZEB2 binding by chromatin immunoprecipitation-sequencing (ChIP-seq) under endogenous ZEB2 expression conditions...
March 7, 2018: Cellular Oncology (Dordrecht)
Elena A Pudova, Anna V Kudryavtseva, Maria S Fedorova, Andrew R Zaretsky, Dmitry S Shcherbo, Elena N Lukyanova, Anatoly Y Popov, Asiya F Sadritdinova, Ivan S Abramov, Sergey L Kharitonov, George S Krasnov, Kseniya M Klimina, Nadezhda V Koroban, Nadezhda N Volchenko, Kirill M Nyushko, Nataliya V Melnikova, Maria A Chernichenko, Dmitry V Sidorov, Boris Y Alekseev, Marina V Kiseleva, Andrey D Kaprin, Alexey A Dmitriev, Anastasiya V Snezhkina
BACKGROUND: Colorectal cancer (CRC) is a common cancer worldwide. The main cause of death in CRC includes tumor progression and metastasis. At molecular level, these processes may be triggered by epithelial-mesenchymal transition (EMT) and necessitates specific alterations in cell metabolism. Although several EMT-related metabolic changes have been described in CRC, the mechanism is still poorly understood. RESULTS: Using CrossHub software, we analyzed RNA-Seq expression profile data of CRC derived from The Cancer Genome Atlas (TCGA) project...
February 9, 2018: BMC Genomics
Peng Chen, Hongxin Liu, Aiwu Hou, Xibo Sun, Bingxuan Li, Jianyi Niu, Lingling Hu
BACKGROUND Epithelial-mesenchymal transition (EMT) is an essential progress for tumor cell invasion to both epithelial and non-epithelial cancers, and zinc finger E-box-binding homeobox 1/2 (ZEB1/2) is a well-known promoter of EMT. In glioma cell lines, both ZEB1 and ZEB2 have been demonstrated to facilitate cancer cell proliferation and invasion with experiments in vitro. However, the clinical significance of ZEB1 and ZEB2 in glioblastoma (GBM) is still controversial. MATERIAL AND METHODS We detected the expression of ZEB1 and ZEB2 in 91 cases of GBM with immunohistochemistry and investigated the correlation between clinicopathological factors and ZEB family expression with Fisher test...
February 24, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Bin Zhao, Lei Liu, Jun Mao, Zhiwei Zhang, Qifei Wang, Quanlin Li
Emerging evidence has shown that the PIM serine/threonine kinase family, including PIM1, PIM2 and PIM3, is associated with tumour progression towards metastasis. PIM1, an attractive molecular target, has been identified as a potential prognostic biomarker for haematological and epithelial malignancies. However, to date, the potential regulatory roles and molecular mechanisms by which PIM1 affects the development and progression of cancers, including clear-cell renal-cell carcinoma (ccRCC), remain largely unknown...
February 22, 2018: Cell Death & Disease
Guang-Jie Zhu, Pan-Pan Song, Han Zhou, Xiao-Hui Shen, Jun-Guo Wang, Xiao-Feng Ma, Ya-Jun Gu, Ding-Ding Liu, An-Ning Feng, Xiao-Yun Qian, Xia Gao
Epithelial-mesenchymal transition (EMT) allows neoplastic cells to gain the invasive phenotype and become migratory, which is required for cancer progression and metastasis. In the present study, the expression of EMT-associated biomarkers and their association with clinicopathological parameters in laryngeal squamous cell carcinoma (LSCC) was investigated. E-cadherin, N-cadherin, β-catenin and zinc finger E-box binding homeobox 2 (ZEB2) protein expression was evaluated with immunohistochemistry in a cohort of 76 patients with operable LSCC...
March 2018: Oncology Letters
Xueying Li, Jiaqi Jin, Siyuan Yang, Weizhi Xu, Xianbin Meng, Haiteng Deng, Jun Zhan, Shan Gao, Hongquan Zhang
GATA3 is a transcriptional factor involved in the development of multiple organs. Post translational modifications of GATA3 are critical to its function. Here, we report that GATA3 interacts with and is acetylated by the acetyltransferase CBP. Class I deacetylases HDAC1, HDAC2 and HDAC3 deacetylate GATA3. The major acetylated site of GATA3 in lung adenocarcinoma cells was determined at lysine 119 (AcK119). Functionally, GATA3-acetylation mimics K119Q mutant was found to inhibit lung adenocarcinoma cell migration and invasion with concomitant downregulation of EMT-controlling transcriptional factors Slug, Zeb1 and Zeb2...
February 14, 2018: Biochemical and Biophysical Research Communications
Tianxia Guan, Claudia X Dominguez, Robert A Amezquita, Brian J Laidlaw, Jijun Cheng, Jorge Henao-Mejia, Adam Williams, Richard A Flavell, Jun Lu, Susan M Kaech
Long-term immunity depends partly on the establishment of memory CD8 + T cells. We identified a counterregulatory network between the homologous transcription factors ZEB1 and ZEB2 and the miR-200 microRNA family, which modulates effector CD8 + T cell fates. Unexpectedly, Zeb1 and Zeb2 had reciprocal expression patterns and were functionally uncoupled in CD8 + T cells. ZEB2 promoted terminal differentiation, whereas ZEB1 was critical for memory T cell survival and function. Interestingly, the transforming growth factor β (TGF-β) and miR-200 family members, which counterregulate the coordinated expression of Zeb1 and Zeb2 during the epithelial-to-mesenchymal transition, inversely regulated Zeb1 and Zeb2 expression in CD8 + T cells...
February 15, 2018: Journal of Experimental Medicine
Jae Ho Sim, Fei Tian, Soo Yeon Jung, Joong-Hyuck Auh, Hyang Sook Chun
Early detection of the zearalenone (ZEA) chemotype of Fusarium species could be a precautionary measure for preventing ZEA contamination in rice. In this study, a multiplex polymerase chain reaction (mPCR) assay for detecting ZEA-producing fungi in rice was established using a set of four primers targeting the ZEA biosynthesis genes PKS3, PKS13, ZEB1, and ZEB2. Two mPCR approaches were used: one that amplified the DNA obtained from Fusarium isolates (conventional method) and another that directly amplified the target DNA from rice samples without time-consuming DNA isolation (direct method)...
February 3, 2018: International Journal of Food Microbiology
Dongjoon Ko, Semi Kim
Epithelial-mesenchymal transition (EMT) is a process implicated in tumor invasion and metastasis. During EMT, epithelial cells undergo molecular changes to acquire mesenchymal phenotypes, which are mediated by EMT-inducing transcription factors. Previously, we showed that ZEB2 cooperates with the transcription factor Sp1 to function as a transcriptional activator of vimentin, integrin α5, and cadherin-11, which promotes cancer cell invasion. We hypothesized that ZEB2, through cooperation with Sp1, would mediate diverse cellular functions beyond EMT and invasion during metastasis...
January 2, 2018: Oncotarget
S N Sunilgowda, Devipriya Nagarajan, Devipriya Nagarajan
Radiotherapy is the most widely used treatment method for average and advanced lung cancer patients. Moreover, the clinical toxicities caused by radiotherapy are categorized into acute radiation pneumonitis and late pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) is a complex physiological process involves many signaling molecules and proteins like adaptor proteins, and transcriptional factors. It was identified as a significant mechanism for fibrosis, wound healing and also cancer. A variety of biomarkers have appeared in radiation-induced lung EMT, some of which are acquired (N-cadherin, vimentin and fibronectin, etc...
February 6, 2018: Current Drug Targets
John Hoon Rim, Se Hee Kim, In Sik Hwang, Soon Sung Kwon, Jieun Kim, Hyun Woo Kim, Min Jung Cho, Ara Ko, Song Ee Youn, Jihun Kim, Young Mock Lee, Hee Jung Chung, Joon Soo Lee, Heung Dong Kim, Jong Rak Choi, Seung-Tae Lee, Hoon-Chul Kang
BACKGROUND: We intended to evaluate diagnostic utility of a targeted gene sequencing by using next generation sequencing (NGS) panel in patients with intractable early-onset epilepsy (EOE) and find the efficient analytical step for increasing the diagnosis rate. METHODS: We assessed 74 patients with EOE whose seizures started before 3 years of age using a customized NGS panel that included 172 genes. Single nucleotide variants (SNVs) and exonic and chromosomal copy number variations (CNVs) were intensively examined with our customized pipeline and crosschecked with commercial or pre-built software...
February 1, 2018: BMC Medical Genomics
Yan Song, Kui Jiang, Shuai Su, Bangmao Wang, Guangxia Chen
The current study aimed to summarize the clinical manifestations and identify the epigenetic mechanisms of gastric mucosa associated lymphoid tissue (MALT) lymphoma, as well as evaluate the long-term effects of Helicobacter pylori (H. pylori) eradication. A total of 122 patients with marginal zone B-cell lymphoma of primary gastric MALT lymphoma were enrolled in the present study. The clinical manifestations of gastric MALT lymphoma, including symptoms, H. pylori state and endoscopic type, were summarized. The response to therapy was evaluated in patients that underwent H...
January 2018: Experimental and Therapeutic Medicine
Ganesan Arunkumar, Arunagiri Kuha Deva Magendhra Rao, Mayakannan Manikandan, Harikrishnan Prasanna Srinivasa Rao, Shanmugam Subbiah, Ramachandran Ilangovan, Avaniyapuram Kannan Murugan, Arasambattu Kannan Munirajan
MicroRNAs (miRNAs) are reported to function as a major component in the cellular signaling circuit, which regulates epithelial-mesenchymal transition (EMT). Dysregulation of the microRNA-200 (miR-200) family and EMT-associated genes enables tumor metastasis and resistance to therapy. The present study profiled miR-200 family members miR-200a, miR-200b, miR-200c, miR-141 and miR-429, and also several EMT-regulatory genes including zinc finger E-box-binding homeobox (ZEB)1, ZEB2, epithelial cadherin and vimentin in 40 oral primary tumors in order to understand their role(s) in oral squamous cell carcinoma (OSCC)...
January 2018: Oncology Letters
JeongGoo Lee, Eric Jung, Martin Heur
Investigating stimulation of endogenous wound healing in corneal endothelial cells (CECs) may help address the global shortage of donor corneas by decreasing the number of transplants performed for blindness due to endothelial dysfunction.  We previously reported that IL-1β stimulation leads to fibroblast growth factor (FGF2) expression, enhancing migration and proliferation of mammalian CECs.  However, FGF2 also promotes the endothelial-mesenchymal transition, which can lead to retrocorneal membrane formation and blindness...
January 23, 2018: Journal of Biological Chemistry
José Luis Moreno-Amador, Noèlia Téllez, Sandra Marin, Caterina Aloy-Reverté, Carlos Semino, Montserrat Nacher, Eduard Montanya
BACKGROUND: β-cells undergo an epithelial to mesenchymal transition (EMT) when expanded in monolayer culture and give rise to highly proliferative mesenchymal cells that retain the potential to re-differentiate into insulin-producing cells. OBJECTIVE: To investigate whether EMT takes place in the endocrine non-β cells of human islets. METHODOLOGY: Human islets isolated from 12 multiorgan donors were dissociated into single cells, purified by magnetic cell sorting, and cultured in monolayer...
2018: PloS One
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