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

Hyeyoung Nam; Anirban Kundu; Garrett J. Brinkley; Darshan S. Chandrashekar; Richard L. Kirkman; Balabhadrapatruni V.S.K. Chakravarthi; Rachael M. Orlandella; Lyse A. Norian; Guru Sonpavde; Pooja Ghatalia; Fei Fei; Shi Wei; Sooryanarayana Varambally; Sunil Sudarshan

doi:10.1016/j.matbio.2020.01.001

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

Hyeyoung Nam
, Anirban Kundu
, Garrett J. Brinkley
, Darshan S. Chandrashekar
, Richard L. Kirkman
, Balabhadrapatruni V.S.K. Chakravarthi
, Rachael M. Orlandella
, Lyse A. Norian
, Guru Sonpavde
, Pooja Ghatalia
, Fei Fei
, Shi Wei
, Sooryanarayana Varambally
, Sunil Sudarshan

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	43-58
Number of pages	16
Journal	Matrix Biology
Volume	89
DOIs	https://doi.org/10.1016/j.matbio.2020.01.001
State	Published - Jul 2020

Bibliographical note

Publisher Copyright:
© 2020

Funding

This work was supported by Department of Veteran Affairs grant BX002930 and NCI R01 CA200653 (S.S). Research reported in this publication was also supported by the NIH ( P30 CA013148 ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There are no conflicts of interest. We would like to acknowledge Eddy Yang and Debbie Della Manna for assistance with miRNA profiling. Array data were generated by the UT Health San Antonio Cancer Center Genomics Shared Resource.

Funders	Funder number
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	R21CA223126, R01CA200653, R01CA181088, P30CA013148
U.S. Department of Veterans Affairs	BX002930, I01BX002930

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Kidney cancer
PGC1α
SNAIL

ASJC Scopus subject areas

Molecular Biology

Access to Document

10.1016/j.matbio.2020.01.001

Cite this

Nam, H., Kundu, A., Brinkley, G. J., Chandrashekar, D. S., Kirkman, R. L., Chakravarthi, B. V. S. K., Orlandella, R. M., Norian, L. A., Sonpavde, G., Ghatalia, P., Fei, F., Wei, S., Varambally, S., & Sudarshan, S. (2020). PGC1α suppresses kidney cancer progression by inhibiting collagen-induced SNAIL expression. Matrix Biology, 89, 43-58. https://doi.org/10.1016/j.matbio.2020.01.001

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title = "PGC1α suppresses kidney cancer progression by inhibiting collagen-induced SNAIL expression",

abstract = "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.",

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note = "Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = jul,

doi = "10.1016/j.matbio.2020.01.001",

language = "English",

volume = "89",

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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

PY - 2020/7

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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.

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KW - PGC1α

KW - SNAIL

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

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