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

Producción científica: Article › revisión exhaustiva

20 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	43-58
Número de páginas	16
Publicación	Matrix Biology
Volumen	89
DOI	https://doi.org/10.1016/j.matbio.2020.01.001
Estado	Published - jul 2020

Nota bibliográfica

Publisher Copyright:
© 2020

Financiación

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.

Financiadores	Número del financiador
National Institutes of Health (NIH)
National Childhood Cancer Registry – National Cancer Institute	R21CA223126, R01CA200653, R01CA181088, P30CA013148
U.S. Department of Veterans Affairs	BX002930, I01BX002930

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Molecular Biology

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10.1016/j.matbio.2020.01.001

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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

@article{d889441fff7a45dfaf9c9b6f95e608fe,

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.",

keywords = "Kidney cancer, PGC1α, SNAIL",

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

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

year = "2020",

month = jul,

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

language = "English",

volume = "89",

pages = "43--58",

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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

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

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DO - 10.1016/j.matbio.2020.01.001

M3 - Article

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AN - SCOPUS:85079905078

SN - 0945-053X

VL - 89

SP - 43

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JO - Matrix Biology

JF - Matrix Biology

ER -

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

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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