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Your search keyword '"Epithelial-tomesenchymal transition"' showing total 2 results
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2 results on '"Epithelial-tomesenchymal transition"'

1. Clear Cell Renal Cell Carcinoma is linked to Epithelial-to-Mesenchymal Transition and to Fibrosis.

Author

Landolt, Lea, Eikrem, Øystein, Strauss, Philipp, Scherer, Andreas, Lovett, David H., Beisland, Christian, Finne, Kenneth, Osman, Tarig, Ibrahim, Mohammad M., Gausdal, Gro, Ahmed, Lavina, Lorens, James B., Thiery, Jean Paul, Tan, Tuan Zea, Sekulic, Miroslav, and Marti, Hans‐Peter

Subjects
*RENAL cell carcinoma, *LIQUID chromatography-mass spectrometry, *IMMUNOHISTOCHEMISTRY, *MICRORNA, *GENE expression, *DIAGNOSIS
Abstract

Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients (n = 26) undergoing partial or radical nephrectomy due to ccRCC. RNA sequencing libraries were generated using Illumina TruSeq® Access library preparation protocol and TruSeq Small RNA library preparation kit. Next generation sequencing (NGS) was performed on Illumina HiSeq2500. Comparative analysis of matched sample pairs was done using the Bioconductor Limma/voom R-package. Liquid chromatography-tandem mass spectrometry and immunohistochemistry were applied to measure and visualize protein abundance. We detected an increased generic EMT transcript score in ccRCC. Gene expression analysis showed augmented abundance of AXL and MMP14, as well as downregulated expression of KL (klotho). Moreover, microRNA analyses demonstrated a positive expression correlation of miR-34a and its targets MMP14 and AXL. Survival analysis based on a subset of genes from our list EMTrelated genes in a publicly available dataset showed that the EMT genes correlated with ccRCC patient survival. Several of these genes also play a known role in fibrosis. Accordingly, recently published classifiers of solid organ fibrosis correctly identified EMT-affected tumor samples and were correlated with patient survival. EMT in ccRCC linked to fibrosis is associated with worse survival and may represent a target for novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Published
2017
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2. Inhibition of p38 mitogen-activated protein kinase alters microRNA expression and reverses epithelial-to-mesenchymal transition

Author

Seungyoon Nam, Bridgette M. Collins-Burow, James W. Antoon, Virgilo A. Salvo, Steven Elliott, Kenneth P. Nephew, Ashley M. Nitzchke, Lyndsay V. Rhodes, Scott A. Wadsworth, Elizabeth C. Martin, and Matthew E. Burow

Subjects
MAPK/ERK pathway, Cancer Research, Epithelial-Mesenchymal Transition, Cell Survival, MAP Kinase Signaling System, Pyridines, Gene Expression, Antineoplastic Agents, Breast Neoplasms, Biology, medicine.disease_cause, p38 Mitogen-Activated Protein Kinases, drug discovery, Mice, 03 medical and health sciences, breast cancer, 0302 clinical medicine, microRNA, Gene expression, medicine, Animals, Cluster Analysis, Humans, Epithelial–mesenchymal transition, Protein kinase A, 030304 developmental biology, 0303 health sciences, Oncogene, Tumor Necrosis Factor-alpha, Imidazoles, p38 mitogen-activated protein kinase, Articles, epithelial-tomesenchymal transition, Cell cycle, Xenograft Model Antitumor Assays, 3. Good health, MicroRNAs, Cell Transformation, Neoplastic, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, MCF-7 Cells, Cancer research, Female, Transcriptome, Carcinogenesis
Abstract

Acquired chemoresistance and epithelial-to-mesenchymal transition (EMT) are hallmarks of cancer progression and of increasing clinical relevance. We investigated the role of miRNA and p38 mitogen-activated protein kinase (MAPK) signaling in the progression of breast cancer to a drug-resistant and mesenchymal phenotype. We demonstrate that acquired death receptor resistance results in increased hormone-independent tumorigenesis compared to hormone-sensitive parental cells. Utilizing global miRNA gene expression profiling, we identified miRNA alterations associated with the development of death receptor resistance and EMT progression. We further investigated the role of p38 MAPK in this process, showing dose-dependent inactivation of p38 by its inhibitor RWJ67657 and decreased downstream ATF and NF‑κB signaling. Pharmacological inhibition of p38 also decreased chemoresistant cancer tumor growth in xenograft animal models. Interestingly, inhibition of p38 partially reversed the EMT changes found in this cell system, as illustrated by decreased gene expression of the EMT markers Twist, Snail, Slug and ZEB and protein and mRNA levels of Twist, a known EMT promoter, concomitant with decreased N‑cadherin protein. RWJ67657 treatment also altered the expression of several miRNAs known to promote therapeutic resistance, including miR‑200, miR‑303, miR‑302, miR‑199 and miR‑328. Taken together, our results demonstrate the roles of multiple microRNAs and p38 signaling in the progression of cancer and demonstrate the therapeutic potential of targeting the p38 MAPK pathway for reversing EMT in an advanced tumor phenotype.

Published
2013
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