PIM1 mediates epithelial-mesenchymal transition by targeting Smads and c-Myc in the nucleus and potentiates clear-cell renal-cell carcinoma oncogenesis.

Cell Death & Disease
Bin ZhaoQuanlin Li

Abstract

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. Herein, we present the first evidence that PIM1 is aberrantly overexpressed in human ccRCC tissues and cell lines and positively correlated with human ccRCC progression. In our study, depletion of PIM1 attenuated ccRCC cell proliferation, colony formation, migration, invasion and angiogenesis, suggesting that PIM1 expression may be a cancer-promoting event in ccRCC. Mechanistically, we observed that PIM1 could interact with Smad2 or Smad3 in the nucleus and subsequently phosphorylate Smad2 and Smad3 to induce the expression of transcription factors, including ZEB1, ZEB2, Snail1, Snail2 and Twist, to promote epithelial-mesenchymal transition (EMT). In addition, PIM1-mediated phosphorylation of c-Myc activates the expres...Continue Reading

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Citations

Sep 13, 2019·Science Translational Medicine·Ann LinJason M Sheltzer
Jun 20, 2020·The Journal of Pathology·Ming-Sum LeungRegina Cheuk-Lam Lo
Apr 17, 2019·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Xueqiang GaoHaibo Wang
Jul 19, 2018·Journal of Experimental & Clinical Cancer Research : CR·Xiupeng XuJing Ji
Oct 22, 2020·International Journal of Molecular Sciences·Erna Marija MeškytėYari Ciribilli
Mar 17, 2020·Cardiovascular Research·David E EbeidMark A Sussman
Oct 19, 2020·Current Cancer Drug Targets·Milad AshrafizadehManoj Garg
Aug 28, 2021·Biomedicines·Ekaterina Mikhailovna StasevichAnton Markovich Schwartz

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Methods Mentioned

BETA
surgical resection
co-IP
co-immunoprecipitation
fluorescence microscopy
PCR
protein assay

Software Mentioned

SPSS
ImageJ

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