PGC1α suppresses kidney cancer progression by inhibiting collagen-induced SNAIL expression.

Autor: Nam H; Department of Urology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Kundu A; Department of Urology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Brinkley GJ; Department of Urology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Chandrashekar DS; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Kirkman RL; Department of Urology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Chakravarthi BVSK; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Orlandella RM; Graduate Biomedical Science, Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Norian LA; Department of Nutrition Sciences, Nutrition Obesity Research Center, University of Alabama at Birmingham, AL, 35294, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35233, USA., Sonpavde G; Department of Medical Oncology, Dana Farber Cancer Institute, MA, 02215, USA., Ghatalia P; Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA., Fei F; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA., Wei S; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35233, USA., Varambally S; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35233, USA., Sudarshan S; Department of Urology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA; Birmingham Veterans Affairs Medical Center, Birmingham, AL, 35233, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. Electronic address: sudarshan@uab.edu.
Jazyk: angličtina
Zdroj: Matrix biology : journal of the International Society for Matrix Biology [Matrix Biol] 2020 Jul; Vol. 89, pp. 43-58. Date of Electronic Publication: 2020 Jan 23.
DOI: 10.1016/j.matbio.2020.01.001
Abstrakt: The transcriptional events that promote invasive and metastatic phenotypes in renal cell carcinoma (RCC) remain poorly understood. Here we report that the decreased expression of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α) and the increased expression of several genes encoding collagen family members are associated with RCC tumor progression. PGC1α restoration attenuates invasive phenotypes and suppresses tumor progression in vivo. In contrast, collagens produced by RCC cells promote invasive and migratory phenotypes. PGC1α restoration suppresses the expression of collagens and tumor phenotypes via the induction of miR-29a. Furthermore, decreased collagens via the PGC1α/miR-29a axis suppresses collagen-mediated activation of discoidin domain receptor 1 (DDR1)/ERK signaling. In turn, the suppression of collagen/DDR1 signaling by PGC1α leads to decreased levels of the known EMT regulators SNAIL1 and 2. Collectively, our results demonstrate a novel role for PGC1α in the regulation of proinvasive SNAIL proteins.
Competing Interests: Declaration of Interests The authors declare no competing interests.
(Published by Elsevier B.V.)
Databáze: MEDLINE
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