RNF208, an estrogen-inducible E3 ligase, targets soluble Vimentin to suppress metastasis in triple-negative breast cancers

Kyoungwha Pang, Jinah Park, Sung Gwe Ahn, Jihee Lee, Yuna Park, Akira Ooshima, Seiya Mizuno, Satoshi Yamashita, Kyung Soon Park, So Young Lee, Joon Jeong, Toshikazu Ushijima, Kyung Min Yang, Seong Jin Kim

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2 Citations (Scopus)

Abstract

The development of triple-negative breast cancer (TNBC) negatively impacts both quality of life and survival in a high percentage of patients. Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells. RNF208 was significantly lower in TNBC than the luminal type, and low expression of RNF208 was strongly associated with poor clinical outcomes. Furthermore, RNF208 was induced by 17β-estradiol (E2) treatment in an estrogen receptor alpha (ΕRα)-dependent manner. Overexpression of RNF208 suppresses tumor formation and lung metastasis of TNBC cells. Mechanistically, RNF208 specifically polyubiquitinated the Lys97 residue within the head domain of Vimentin through interaction with the Ser39 residue of phosphorylated Vimentin, which exists as a soluble form, eventually facilitating proteasomal degradation of Vimentin. Collectively, our findings define RNF208 as a negative regulator of soluble Vimentin and a prognostic biomarker for TNBC cells.

Original languageEnglish
Article number5805
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Pang, K., Park, J., Ahn, S. G., Lee, J., Park, Y., Ooshima, A., Mizuno, S., Yamashita, S., Park, K. S., Lee, S. Y., Jeong, J., Ushijima, T., Yang, K. M., & Kim, S. J. (2019). RNF208, an estrogen-inducible E3 ligase, targets soluble Vimentin to suppress metastasis in triple-negative breast cancers. Nature communications, 10(1), [5805]. https://doi.org/10.1038/s41467-019-13852-5