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PBRM1 deficiency oncogenic addiction is associated with activated AKT-mTOR signalling and aerobic glycolysis in clear cell renal cell carcinoma cells.
Tang, Yu; Jin, Yan-Hong; Li, Hu-Li; Xin, Hui; Chen, Jin-Dong; Li, Xue-Ying; Pan, You-Fu.
Afiliación
  • Tang Y; Department of Medical Genetics, Zunyi Medical University, Zunyi, China.
  • Jin YH; Key Laboratory of Gene Detection and Treatment in Guizhou Province, Zunyi, China.
  • Li HL; Department of Medical Genetics, Zunyi Medical University, Zunyi, China.
  • Xin H; Key Laboratory of Gene Detection and Treatment in Guizhou Province, Zunyi, China.
  • Chen JD; Department of Medical Genetics, Zunyi Medical University, Zunyi, China.
  • Li XY; Department of Medical Genetics, Zunyi Medical University, Zunyi, China.
  • Pan YF; Key Laboratory of Gene Detection and Treatment in Guizhou Province, Zunyi, China.
J Cell Mol Med ; 26(14): 3837-3849, 2022 07.
Article en En | MEDLINE | ID: mdl-35672925
The PBRM1 (PB1) gene which encodes the specific subunit BAF180 of the PBAF SWI/SNF complex, is highly mutated (~ 40%) in clear cell renal cell carcinoma (ccRCC). However, its functions and impact on cell signalling are still not fully understood. Aerobic glycolysis, also known as the 'Warburg Effect', is a hallmark of cancer, whether PB1 is involved in this metabolic shift in clear cell renal cell carcinoma remains unclear. Here, with established stable knockdown PB1 cell lines, we performed functional assays to access the effects on 786-O and SN12C cells. Based on the RNA-seq data, we selected some genes encoding key glycolytic enzymes, including PFKP, ENO1, PKM and LDHA, and examined the expression levels. The AKT-mTOR signalling pathway activity and expression of HIF1α were also analysed. Our data demonstrate that PB1 deficiency promotes the proliferation, migration, Xenograft growth of 786-O and SN12C cells. Notably, knockdown of PB1 activates AKT-mTOR signalling and increases the expression of key glycolytic enzymes at both mRNA and protein levels. Furthermore, we provide evidence that deficient PB1 and hypoxic conditions exert a synergistic effect on HIF 1α expression and lactate production. Thus, our study provides novel insights into the roles of tumour suppressor PB1 and suggests that the AKT-mTOR signalling pathway, as well as glycolysis, is a potential drug target for ccRCC patients with deficient PB1.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Carcinoma de Células Renales / Proteínas de Unión al ADN / Neoplasias Renales Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Carcinoma de Células Renales / Proteínas de Unión al ADN / Neoplasias Renales Tipo de estudio: Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido