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Nam H , Kundu A , Brinkley GJ , Chandrashekar DS , Kirkman RL , Chakravarthi BVSK , Orlandella RM , Norian LA , Sonpavde G , Ghatalia P , Fei F , Wei S , Varambally S , Sudarshan S
PGC1alpha suppresses kidney cancer progression by inhibiting collagen-induced SNAIL expression
Matrix Biology. 2020 Jul;89 :43-58
PMID: 31982456    PMCID: PMC7712461    URL: https://www.ncbi.nlm.nih.gov/pubmed/31982456
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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 (PGC1alpha) and the increased expression of several genes encoding collagen family members are associated with RCC tumor progression. PGC1alpha restoration attenuates invasive phenotypes and suppresses tumor progression in vivo. In contrast, collagens produced by RCC cells promote invasive and migratory phenotypes. PGC1alpha restoration suppresses the expression of collagens and tumor phenotypes via the induction of miR-29a. Furthermore, decreased collagens via the PGC1alpha/miR-29a axis suppresses collagen-mediated activation of discoidin domain receptor 1 (DDR1)/ERK signaling. In turn, the suppression of collagen/DDR1 signaling by PGC1alpha leads to decreased levels of the known EMT regulators SNAIL1 and 2. Collectively, our results demonstrate a novel role for PGC1alpha in the regulation of proinvasive SNAIL proteins.
Export Date: 1 April 2020 Matrix Biol. 2020 Jul;89:43-58. doi: 10.1016/j.matbio.2020.01.001. Epub 2020 Jan 23.