STAT3-mediated MLST8 gene expression regulates cap-dependent translation in cancer cells

Hyunji Lee, Hyunjung Chin, Hyeyoung Kim, Hosung Jung, Daekee Lee

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish
Pages (from-to)1850-1867
Number of pages18
JournalMolecular Oncology
Issue number8
StatePublished - 1 Aug 2020

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (2018R1D1A1B07048622 and 2014M3A9D5A0107512832).

Publisher Copyright:
© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.


  • 4E-BP1
  • MLST8
  • STAT3
  • cross-talk
  • mTORC1


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