PGC1α Suppresses Kidney Cancer Progression by Inhibiting Collagen-induced SNAIL Expression

Overview

Journal Matrix Biol

Publisher Elsevier

Specialties Biochemistry
Molecular Biology

Date 2020 Jan 27

PMID 31982456

Citations 11

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

ITGA3 promotes pancreatic cancer progression through HIF1α- and c-Myc-driven glycolysis in a collagen I-dependent autocrine manner.

Li R, Ji Q, Fu S, Gu J, Liu D, Wang L Cancer Gene Ther. 2024; 32(2):240-253.

PMID: 39690180 DOI: 10.1038/s41417-024-00864-7.

The role of circular RNA targeting IGF2BPs in cancer-a potential target for cancer therapy.

Luo X, Shi J, Wang S, Jin X J Mol Med (Berl). 2024; 102(11):1297-1314.

PMID: 39287635 DOI: 10.1007/s00109-024-02488-8.

From metabolism to malignancy: the multifaceted role of PGC1α in cancer.

Wang Y, Peng J, Yang D, Xing Z, Jiang B, Ding X Front Oncol. 2024; 14:1383809.

PMID: 38774408 PMC: 11106418. DOI: 10.3389/fonc.2024.1383809.

Evidence That DDR1 Promotes Oligodendrocyte Differentiation during Development and Myelin Repair after Injury.

Mei R, Qiu W, Yang Y, Xu S, Rao Y, Li Q Int J Mol Sci. 2023; 24(12).

PMID: 37373466 PMC: 10299687. DOI: 10.3390/ijms241210318.

Circular RNA circ-TNPO3 inhibits clear cell renal cell carcinoma metastasis by binding to IGF2BP2 and destabilizing SERPINH1 mRNA.

Pan X, Huang B, Ma Q, Ren J, Liu Y, Wang C Clin Transl Med. 2022; 12(7):e994.

PMID: 35876041 PMC: 9309750. DOI: 10.1002/ctm2.994.

References

Handschin C, Spiegelman B . The role of exercise and PGC1alpha in inflammation and chronic disease. Nature. 2008; 454(7203):463-9. PMC: 2587487. DOI: 10.1038/nature07206. View

Nam H, Chandrashekar D, Kundu A, Shelar S, Kho E, Sonpavde G . Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis. Mol Cancer Res. 2018; 17(1):84-96. PMC: 7222224. DOI: 10.1158/1541-7786.MCR-17-0636. View

Fu H, Valiathan R, Arkwright R, Sohail A, Mihai C, Kumarasiri M . Discoidin domain receptors: unique receptor tyrosine kinases in collagen-mediated signaling. J Biol Chem. 2013; 288(11):7430-7437. PMC: 3597784. DOI: 10.1074/jbc.R112.444158. View

Nishikawa R, Chiyomaru T, Enokida H, Inoguchi S, Ishihara T, Matsushita R . Tumour-suppressive microRNA-29s directly regulate LOXL2 expression and inhibit cancer cell migration and invasion in renal cell carcinoma. FEBS Lett. 2015; 589(16):2136-45. DOI: 10.1016/j.febslet.2015.06.005. View

Chandrashekar D, Bashel B, Balasubramanya S, Creighton C, Ponce-Rodriguez I, Chakravarthi B . UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia. 2017; 19(8):649-658. PMC: 5516091. DOI: 10.1016/j.neo.2017.05.002. View

Haq R, Shoag J, Andreu-Perez P, Yokoyama S, Edelman H, Rowe G . Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF. Cancer Cell. 2013; 23(3):302-15. PMC: 3635826. DOI: 10.1016/j.ccr.2013.02.003. View

Castoldi G, Di Gioia C, Bombardi C, Catalucci D, Corradi B, Gualazzi M . MiR-133a regulates collagen 1A1: potential role of miR-133a in myocardial fibrosis in angiotensin II-dependent hypertension. J Cell Physiol. 2011; 227(2):850-6. DOI: 10.1002/jcp.22939. View

Kwiecinski M, Noetel A, Elfimova N, Trebicka J, Schievenbusch S, Strack I . Hepatocyte growth factor (HGF) inhibits collagen I and IV synthesis in hepatic stellate cells by miRNA-29 induction. PLoS One. 2011; 6(9):e24568. PMC: 3170366. DOI: 10.1371/journal.pone.0024568. View

LeBleu V, OConnell J, Gonzalez Herrera K, Wikman H, Pantel K, Haigis M . PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nat Cell Biol. 2014; 16(10):992-1003, 1-15. PMC: 4369153. DOI: 10.1038/ncb3039. View

10.

Gyorfi A, Matei A, Distler J . Targeting TGF-β signaling for the treatment of fibrosis. Matrix Biol. 2018; 68-69:8-27. DOI: 10.1016/j.matbio.2017.12.016. View

11.

Lin J, Handschin C, Spiegelman B . Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. 2005; 1(6):361-70. DOI: 10.1016/j.cmet.2005.05.004. View

12.

Jedeszko C, Paez-Ribes M, Di Desidero T, Man S, Lee C, Xu P . Postsurgical adjuvant or metastatic renal cell carcinoma therapy models reveal potent antitumor activity of metronomic oral topotecan with pazopanib. Sci Transl Med. 2015; 7(282):282ra50. DOI: 10.1126/scitranslmed.3010722. View

13.

Chen L, Qu C, Chen H, Xu L, Qi Q, Luo J . Chinese herbal medicine suppresses invasion-promoting capacity of cancer-associated fibroblasts in pancreatic cancer. PLoS One. 2014; 9(4):e96177. PMC: 4004556. DOI: 10.1371/journal.pone.0096177. View

14.

Hosein A, Livingstone J, Buchanan M, Reid J, Hallett M, Basik M . A functional in vitro model of heterotypic interactions reveals a role for interferon-positive carcinoma associated fibroblasts in breast cancer. BMC Cancer. 2015; 15:130. PMC: 4369836. DOI: 10.1186/s12885-015-1117-0. View

15.

Shrivastava A, Radziejewski C, Campbell E, Kovac L, McGlynn M, Ryan T . An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors. Mol Cell. 1998; 1(1):25-34. DOI: 10.1016/s1097-2765(00)80004-0. View

16.

Ji J, Zhao L, Budhu A, Forgues M, Jia H, Qin L . Let-7g targets collagen type I alpha2 and inhibits cell migration in hepatocellular carcinoma. J Hepatol. 2010; 52(5):690-7. PMC: 2862772. DOI: 10.1016/j.jhep.2009.12.025. View

17.

Cen L, Liu W, Cui L, Zhang W, Cao Y . Collagen tissue engineering: development of novel biomaterials and applications. Pediatr Res. 2008; 63(5):492-6. DOI: 10.1203/PDR.0b013e31816c5bc3. View

18.

Valiathan R, Marco M, Leitinger B, Kleer C, Fridman R . Discoidin domain receptor tyrosine kinases: new players in cancer progression. Cancer Metastasis Rev. 2012; 31(1-2):295-321. PMC: 3351584. DOI: 10.1007/s10555-012-9346-z. View

19.

Vogel W, Gish G, Alves F, Pawson T . The discoidin domain receptor tyrosine kinases are activated by collagen. Mol Cell. 1998; 1(1):13-23. DOI: 10.1016/s1097-2765(00)80003-9. View

20.

Chakravarthi B, Goswami M, Pathi S, Robinson A, Cieslik M, Chandrashekar D . MicroRNA-101 regulated transcriptional modulator SUB1 plays a role in prostate cancer. Oncogene. 2016; 35(49):6330-6340. PMC: 5140777. DOI: 10.1038/onc.2016.164. View