RT Journal Article
T1 c-MYB- and PGC1a-dependent metabolic switch induced by MYBBP1A loss in renal cancer.
A1 Felipe-Abrio, Blanca
A1 Verdugo-Sivianes, Eva M
A1 Carnero, Amancio
K1 MYBBP1A
K1 PGC1α
K1 c-MYB
K1 metabolism
K1 renal cancer
AB The tumor microenvironment may alter the original tumorigenic potential of tumor cells. Under harsh environmental conditions, genetic alterations conferring selective advantages may initiate the growth of tumor subclones, providing new opportunities for these tumors to grow. We performed a genetic loss-of-function screen to identify genetic alterations able to promote tumor cell growth in the absence of glucose. We identified that downregulation of MYBBP1A increases tumorigenic properties under nonpermissive conditions. MYBBP1A downregulation simultaneously activates PGC1α, directly by alleviating direct repression and indirectly by increasing PGC1α mRNA levels through c-MYB, leading to a metabolic switch from glycolysis to OXPHOS and increased tumorigenesis in low-glucose microenvironments. We have also identified reduced MYBBP1A expression in human renal tumor samples, which show high expression levels of genes involved in oxidative metabolism. In summary, our data support the role of MYBBP1A as a tumor suppressor by regulating c-MYB and PGC1α. Therefore, loss of MYBBP1A increases adaptability spanning of tumors through metabolic switch.
PB John Wiley & Sons Ltd.
YR 2019
FD 2019-06-11
LK http://hdl.handle.net/10668/13927
UL http://hdl.handle.net/10668/13927
LA en
NO Felipe-Abrio B, Verdugo-Sivianes EM, Carnero A. c-MYB- and PGC1a-dependent metabolic switch induced by MYBBP1A loss in renal cancer. Mol Oncol. 2019 Jul;13(7):1519-1533.
NO The authors thank Dr Ricardo Pardal, Dr Julian Aragones and Dr Sandra Muñoz Galván for critical reading of this manuscript. The AC laboratory was supported by grants from the Spanish Ministry of Science, Innovation and Universities, Plan Estatal de I+D+I 2018 cofunded by FEDER, RTI2018-097455-B-I00; the Spanish Ministry of Economy and Competitivity, Plan Estatal de I+D+I 2013-2016, ISCIII (Fis: PI15/00045) and CIBER de Cáncer (CB16/12/00275), cofunded by FEDER from Regional Development European Funds (European Union), Consejería de Ciencia e Innovación (CTS-1848), and Consejería de Salud of the Junta de Andalucía (PI-0096-2014). This work was possible thanks to the Fundacion BBVA, Fundacion AECC, and the Grant PIE13/0004 funded by the ISCIII and FEDER Funds. BF-A is funded by the Spanish Ministry of Education (FPU12/01380).
DS RISalud
RD Apr 6, 2025