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EMT renal

Chang Liu, Tatiana Shaurova, Suzanne Shoemaker, Martin Petkovich, Pamela A Hershberger, Yun Wu
Mutation in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene drives the development of lung cancer. EGFR tyrosine kinase inhibitors (EGFR TKI) including erlotinib and afatinib are initially effective in treating EGFR mutant non-small cell lung cancer (NSCLC). However, drug resistance quickly develops due to several mechanisms, including induction of the epithelial-mesenchymal transition (EMT). No effective therapies are currently available for patients who develop EMT-associated EGFR TKI resistance...
June 14, 2018: Molecular Pharmaceutics
Huayi Li, Xingwen Wang, Cheng Zhang, Yiwei Cheng, Miao Yu, Kunming Zhao, Wenjie Ge, Anyong Cai, Yao Zhang, Fengtong Han, Ying Hu
Renal cell carcinoma (RCC) is highly resistant to chemotherapies. The lack of efficacious treatment for metastatic RCC has led to a poor 5-year survival rate. Here, we found that Apoptosis-stimulating protein of p53-2(ASPP2) was frequently decreased in primary RCC tissues in comparison with non-tumoural kidney controls. Decreased ASPP2 was correlated with high grades and poor outcomes of RCC. Further studies revealed that ASPP2 downregulation promoted EMT and increased resistance to 5-Fluorouracil (5-FU)-induced apoptosis...
June 8, 2018: Cancer Letters
Shiyue Zhao, Yangwei Wang, Manyu Luo, Wenpeng Cui, Xiaoxi Zhou, Lining Miao
BACKGROUND Data on the expression of RCC tissues from the GEO database and patient survival data from TCGA were used to explore the prognostic significance of long noncoding RNA SNHG1. SNHG1 has been reported to participate in the development of several cancers, but, the underlying mechanism of SNHG1 in renal cell carcinoma (RCC) has not been reported. The purpose of our study was to investigate the potential function of SNHG1 in RCC. MATERIAL AND METHODS The expression of SNHG1 in 40 cases of RCC and adjacent normal tissues and 5 cell lines was detected by qRT-PCR...
June 6, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Wei-Qing Han, Lian Xu, Xiao-Feng Tang, Wen-Dong Chen, Yong-Jie Wu, Ping-Jin Gao
KEY POINTS: Membrane rafts (MRs)-redox signaling pathway is activated in response to TGF-1β stimulation in renal tubular cells. MRs-redox signaling pathway contributes to TGF-1β-induced epithelial-mesenchymal transition (EMT) in renal tubular cells. MRs-redox signaling pathway is activated in renal tubular cells isolated from angiotensin II (AngII)-induced hypertensive rats. Inhibition of MRs-redox signaling pathway attenuated renal inflammation and fibrosis in AngII-induced hypertension...
June 4, 2018: Journal of Physiology
Cedric Lebacle, Aydin Pooli, Thomas Bessede, Jacques Irani, Allan J Pantuck, Alexandra Drakaki
Long recognized to confer an extremely poor prognosis, sarcomatoid dedifferentiation of renal cell carcinoma (sRCC) is a tumor phenotype that is finally beginning to be better understood on the molecular and genetic levels. With an overall incidence that ranges from 1 to 32% depending on associated RCC subtype, the survival of sarcomatoid RCC patients rarely exceeds 2 years. The main reasons for its poor outcome include its aggressive biology, its tendency to present at an advanced or metastatic stage at the time of diagnosis, its high rate of tumor recurrence after nephrectomy, and its limited response to systemic therapies...
June 1, 2018: World Journal of Urology
Nicole Kiweler, Boris Brill, Matthias Wirth, Ines Breuksch, Teresa Laguna, Cornelia Dietrich, Susanne Strand, Günter Schneider, Bernd Groner, Falk Butter, Thorsten Heinzel, Walburgis Brenner, Oliver H Krämer
Novel therapies are required for the treatment of metastatic renal cell carcinoma (RCC), which is associated with inoperable disease and patient death. Histone deacetylases (HDACs) are epigenetic modifiers and potential drug targets. Additional information on molecular pathways that are altered by histone deacetylase inhibitors (HDACi) in RCC cells is warranted. It should equally be delineated further which individual members of the 18 mammalian HDACs determine the survival and tumor-associated gene expression programs of such cells...
May 29, 2018: Archives of Toxicology
Naomi Terada, Mohammad Rabiul Karim, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate
BACKGROUND: β-Catenin is a multi-functional protein involved in nephrogenesis and also plays important roles in renal injury. Here, the expression of β-catenin was investigated in the proximal renal tubular epithelial cells in cisplatin (CDDP)-induced acute kidney injury (AKI) and chronic kidney injury (CKI), because CDDP-induced renal lesions were characterized by proximal renal tubular epithelial degeneration/regeneration and subsequent interstitial fibrosis. METHODS: F344 rats were treated with CDDP...
May 26, 2018: Clinical and Experimental Nephrology
Ola A Harb, Mariem A Elfeky, Basant Sh El Shafaay, Heba F Taha, Gamal Osman, Ibtsam Shehta Harera, Loay M Gertallah, Doaa Metwaly Abdelmonem, Ahmed Embaby
BACKGROUND: Clear cell renal cell carcinoma (cc-RCC), is a serious cancer regarding; its fatality, liability for metastases and chemoresistance, so identification of recent therapeutic targets to improve the patients prognosis is needed. SPOP is a BTB/POZ domain containing speckle-type POZ protein, has been identified as an E3 ubiquitin ligase component. ZEB1 is an essential epithelial mesenchymal transition (EMT) activator; E-cadherin is a cell adhesion protein that had been detected in normal epithelial cells membrane...
May 18, 2018: Pathophysiology: the Official Journal of the International Society for Pathophysiology
Letícia B Sene, Victor Hugo Gonçalves Rizzi, José A R Gontijo, Patricia A Boer
Studies have shown that adult offspring of mothers fed a protein-restricted diet during pregnancy present a pronounced reduction of nephron number associated with decreased fractional urinary sodium excretion and arterial hypertension. Additionally, recent advances in our understanding of the molecular pathways that govern the association of gestational nutritional restriction, intrauterine growth retardation and inflammation with impaired nephrogenesis, nephron underdosing and kidney fibrosis point to the epithelial to mesenchymal transition (EMT) as a common factor...
May 22, 2018: Journal of Experimental Biology
Xiaoxu Zhou, Chongxiang Xiong, Evelyn Tolbert, Ting C Zhao, George Bayliss, Shougang Zhuang
Enhancer of zeste homolog-2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. Its role in renal epithelial-mesenchymal transition (EMT) remains unknown. In this study, we found that EZH2 and H3K27me3 were highly expressed in mouse kidney with unilateral ureteral obstruction and cultured mouse kidney proximal tubular (TKPT) cells undergoing EMT. Inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) attenuated renal fibrosis, which was associated with preserving E-cadherin expression and inhibiting Vimentin up-regulation in the obstructed kidney...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Guang-Wei Zhang, Xin Tian, Yang Li, Zhi-Qiang Wang, Xiao-Dong Li, Chao-Yang Zhu
V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2), belonging to the ETS family of transcription factors, is implicated in a broad range of cellular functions. Recently, ETS2 has been found playing an important role in the progression of some types of cancers. However, it remains unclear whether ETS2 has any effects on renal cell carcinoma (RCC). In this study, we investigated the biological functions of ETS2 in RCC. The results showed that ETS2 was highly expressed in RCC tissues and cell lines and its expression had an association with clinicopathological characteristics of RCC patients...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Tong Zhou, Maocai Luo, Wei Cai, Siyuan Zhou, Danying Feng, Chundi Xu, Hongyan Wang
Renal fibrosis is widely considered a common mechanism leading to end-stage renal failure. Epithelial-to-mesenchymal transition (EMT) plays important roles in the pathogenesis of renal fibrosis. Runt-related transcription factor 1(RUNX1) plays a vital role in hematopoiesis via Endothelial-to-Hematopoietic Transition (EHT), a process that is conceptually similar to EMT, but its role in EMT and renal fibrosis is unclear. Here, we demonstrate that RUNX1 is overexpressed in the processes of TGF-β-induced partial EMT and renal fibrosis and that the expression level of RUNX1 is SMAD3-dependent...
May 11, 2018: EBioMedicine
Isao Matsumoto, James K Chambers, Kazumi Nibe, Ryohei Kinoshita, Ryohei Nishimura, Hiroyuki Nakayama, Kazuyuki Uchida
The biological behavior and immunohistochemical features of feline renal cell carcinoma (RCC) have not been well characterized. In the present study, immunohistochemical examinations were performed in 12 feline cases of RCC. The RCC consisted of solid ( n = 2), solid-tubular ( n = 2), tubular ( n = 3), papillary ( n = 2), tubulopapillary ( n = 2), and sarcomatoid ( n = 1) type lesions. Of the cases with RCC, 1 developed metastatic disease and 6 cases had no evidence of recurrence at 80 to 2292 days after surgery...
January 1, 2018: Veterinary Pathology
Yang Du, Chuize Kong, Yuyan Zhu, Meng Yu, Zeliang Li, Jianbin Bi, Zhenhua Li, Xiankui Liu, Zhe Zhang, Xiuyue Yu
Aberrant expression of long noncoding RNAs (lncRNAs) is associated with cancer tumorigenesis and progression. It has been suggested that lncRNAs may be potential clinical diagnostic and prognostic biomarkers, and therapeutic targets. In the present study, the expression levels of small nucleolar RNA host gene 15 (SNHG15) were significantly upregulated in renal cell carcinoma (RCC) tissues and cell lines compared with in adjacent tissues and a proximal tubule epithelial cell line, as determined by reverse transcription‑quantitative polymerase chain reaction...
May 4, 2018: International Journal of Oncology
Yong Huang, Zhen Zhang, Yanru Huang, Zhimin Mao, Xiawen Yang, Yuki Nakamura, Norifumi Sawada, Takahiko Mitsui, Masayuki Takeda, Jian Yao
Hydrogen sulfide (H2 S), an endogenous gas mediator with multifaced biological functions, has been shown to be effective in the prevention and treatment of renal sclerosis in several models of chronic renal diseases. The mechanisms involved are still unclear. Given that Ang II- and TGF-β-induced renal tubular epithelial-mesenchymal transition (EMT) is a pivotal cellular event leading to renal sclerosis, we examined whether and how H2 S intervened the processes of EMT. Ang II stimulated EMT in renal tubular epithelial cells, as indicated by the increased level of α-smooth muscle actin and a decreased level of E-cadherin...
May 7, 2018: Biochemical and Biophysical Research Communications
Hanqing Hu, Meng Wang, Hongwei Wang, Zheng Liu, Xu Guan, Runkun Yang, Rui Huang, Qingchao Tang, Chaoxia Zou, Guiyu Wang, Xu Gao, Xishan Wang
BACKGROUND/AIMS: Colorectal cancer (CRC) is a malignancy that has high morbidity and mortality and is initiated from accumulative genetic events. Although much effort has been made to elucidate the genetic mechanism underlying this disease, it still remains unknown. Here, we discovered a novel role for multiple epidermal growth factor-like domains protein 6 (MEGF6) in CRC, namely, that it induces the epithelial-to-mesenchymal transition (EMT) to promote CRC metastasis via the transforming growth factor beta (TGFβ)/SMAD signaling pathway...
2018: Cellular Physiology and Biochemistry
Ling Gong, Ling Jiang, Yuanhan Qin, Xingbo Jiang, Kunling Song, Xueyun Yu
Retinoic acid receptor α (RARα), a member of family of the nuclear retinoic acid receptors (RARs), plays an essential role in various chronic kidney diseases (CKD). Renal tubular epithelial to mesenchymal transition (EMT) is a common mechanism of progression of renal interstitial fibrosis (RIF). Hypoxia has been extensively considered as one of major inducers of renal tubular EMT. However, the effects of RARα on hypoxia-induced EMT have not yet been described so far. The aim of the present study was to explore the roles and potential mechanisms of RARα in hypoxia-induced EMT of renal tubular epithelial cells (RTECs)...
May 2, 2018: Cell Biology International
Hao Zhou, Lin Gao, Zuo-Hua Yu, Shi-Jun Hong, Zhi-Wei Zhang, Zhen-Zhen Qiu
OBJECTIVE: To understand the mechanism of long non-coding RNA (LncRNA) HOTAIR on renal interstitial fibrosis (RIF) by regulating Notch1 pathway via the modulation of miR-124. METHODS: Unilateral ureteral occlusion (UUO) was used to construct the RIF rat model. And HK-2 cells induced by TGF-β1 were used for the in vitro experiment, which were divided into five groups: Vehicle, TGF-β1, si-HOTAIR + TGF-β1, miR-124 inhibitor + TGF-β1, and si-HOTAIR+miR-124 inhibitor + TGF-β1 groups...
May 1, 2018: Nephrology
Yong Wang, Donghe Fu, Yajing Chen, Jing Su, Yiting Wang, Xin Li, Wei Zhai, Yuanjie Niu, Dan Yue, Hua Geng
The chronic inflammatory microenvironment within or surrounding the primary renal cell carcinoma (RCC) site promotes oncogenic transformation as well as contributes to the development of metastasis. G3BP stress granule assembly factor 1 (G3BP1) was found to be involved in the regulation of multiple cellular functions. However, its functions in RCC have not been previously explored. Here, we first showed that the expression of G3BP1 is elevated in human RCC and correlates with RCC progression. In cultured RCC cells, knockdown of G3BP1 results in inhibition of tumor cell proliferation, migration, and invasion, consistently with the alteration of epithelial-mesenchymal transition (EMT) and cell proliferative markers, including Cadherins, Vimentin, Snail, Slug, c-Myc, and cyclin D1...
May 2, 2018: Cell Death & Disease
Jiayu Liang, Zhihong Liu, Zijun Zou, Yongquan Tang, Chuan Zhou, Jian Yang, Xin Wei, Yiping Lu
Both epithelial-mesenchymal transition (EMT) and immune regulation are important biological process in malignant tumours. The current research aims to comprehensively explore the potential association between the epithelial-mesenchymal transition (EMT) signature and immune checkpoint signature and its role in predicting the prognosis of clear-cell renal cell carcinoma (ccRCC) patients. EMT-related genes were collected from an experiment-based study and then were investigated using data from the Cancer Genome Atlas...
April 26, 2018: Scientific Reports
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