p53-inducible SESTRINs might play opposite roles in the regulation of early and late stages of lung carcinogenesis.

p53-inducible SESTRINs might play opposite roles in the regulation of early and late stages of lung carcinogenesis. Oncotarget. 2019 Dec 10;10(65):6997-7009 Authors: Ding B, Haidurov A, Chawla A, Parmigiani A, van de Kamp G, Dalina A, Yuan F, Lee JH, Chumakov PM, Grossman SR, Budanov AV Abstract SESTRINs (SESN1-3) are proteins encoded by an evolutionarily conserved gene family that plays an important role in the regulation of cell viability and metabolism in response to stress. Many of the effects of SESTRINs are mediated by negative and positive regulation of mechanistic target of rapamycin kinase complexes 1 and 2 (mTORC1 and mTORC2), respectively, that are often deregulated in human cancers where they support cell growth, proliferation, and cell viability. Besides their effects on regulation of mTORC1/2, SESTRINs also control the accumulation of reactive oxygen species, cell death, and mitophagy. SESN1 and SESN2 are transcriptional targets of tumor suppressor protein p53 and may mediate tumor suppressor activities of p53. Therefore, we conducted studies based on a mouse lung cancer model and human lung adenocarcinoma A549 cells to evaluate the potential impact of SESN1 and SESN2 on lung carcinogenesis. While we observed that expression of SESN1 and SESN2 is often decreased in human tumors, inactivation of Sesn2 in mice positively regulates tumor growth through a mechanism associated with activation of AKT, while knockout of Sesn1 ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research