STAT3-mediated MLST8 gene expression regulates cap-dependent translation in cancer cells
- 주제(키워드) 4E-BP1 , cross-talk , MLST8 , mTORC1 , STAT3
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 John Wiley and Sons Ltd.
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000168769
- 본문언어 영어
- Published As https://dx.doi.org/10.1002/1878-0261.12735
- PubMed https://pubmed.ncbi.nlm.nih.gov/32495998
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Signal transducer and activator of transcription 3 (STAT3) regulates cell growth, cell survival, angiogenesis, metastasis of cancer cells, and cancer immune evasion by regulating gene expression as a transcription factor. However, the effect of STAT3 on translation is almost unknown. We demonstrated that STAT3 acts as a trans-acting factor for MLST8 gene expression and the protein level of mLST8, a core component of mechanistic target of rapamycin complex 1 and 2 (mTORC1/2), positively regulates the mTORC1/2 downstream pathways. Suppression of STAT3 by siRNA attenuated 4E-BP1 phosphorylation, cap-dependent translation, and cell proliferation in a variety of cancer cells. In HCT116 cells, STAT3 knockdown-induced decreases in 4E-BP1 and AKT phosphorylation levels were further attenuated by MLST8 knockdown or recovered by mLST8 overexpression. STAT3 knockdown-induced G2/M phase arrest was partially restored by co-knockdown of 4EBP1, and the attenuation of cell proliferation was enhanced by the expression of an mTORC1-mediated phosphorylation-defective mutant of 4E-BP1. ChIP and promoter mapping using a luciferase reporter assay showed that the −951 to −894 bp of MLST8 promoter seems to include STAT3-binding site. Overall, these results suggest that STAT3-driven MLST8 gene expression regulates cap-dependent translation through 4E-BP1 phosphorylation in cancer cells. © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
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