TY - JOUR
T1 - PGC1α suppresses kidney cancer progression by inhibiting collagen-induced SNAIL expression
AU - Nam, Hyeyoung
AU - Kundu, Anirban
AU - Brinkley, Garrett J.
AU - Chandrashekar, Darshan S.
AU - Kirkman, Richard L.
AU - Chakravarthi, Balabhadrapatruni V.S.K.
AU - Orlandella, Rachael M.
AU - Norian, Lyse A.
AU - Sonpavde, Guru
AU - Ghatalia, Pooja
AU - Fei, Fei
AU - Wei, Shi
AU - Varambally, Sooryanarayana
AU - Sudarshan, Sunil
N1 - Publisher Copyright:
© 2020
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - Kidney cancer
KW - PGC1α
KW - SNAIL
UR - http://www.scopus.com/inward/record.url?scp=85079905078&partnerID=8YFLogxK
U2 - 10.1016/j.matbio.2020.01.001
DO - 10.1016/j.matbio.2020.01.001
M3 - Article
C2 - 31982456
SN - 0945-053X
VL - 89
SP - 43
EP - 58
JO - Matrix Biology
JF - Matrix Biology
ER -
