한빛사 논문
Kyoungwha Pang1,2, Jinah Park1, Sung Gwe Ahn3, Jihee Lee1,2, Yuna Park1,2, Akira Ooshima1, Seiya Mizuno4, Satoshi Yamashita5, Kyung-Soon Park2, So-Young Lee6, Joon Jeong3, Toshikazu Ushijima5, Kyung-Min Yang1,* & Seong-Jin Kim1,7,8,*
1 Precision Medicine Research Center, Advanced Institute of Convergence Technology, Seoul National University, Suwon, Gyeonggi-do 16229, Republic of Korea.
2 Department of Biomedical Science, College of Life Science, CHA University, Seongnam City, Gyeonggi-do 463-400, Republic of Korea.
3 Department of Surgery, Gangnam Severance Hospital, Yonsei University Medical College, 712 Eonjuro, Gangnam-Gu, Seoul 135-720, Republic of Korea.
4 Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
5 Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
6 Department of Internal Medicine, CHA University, Seongnam City, Gyeonggi-do 463-400, Republic of Korea.
7 Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Gyeonggi-do 16229, Republic of Korea.
8 TheragenEtex Bio Institute, TheragenEtex Co, Suwon, Gyeonggi-do 16229, Republic of Korea.
*Correspondence to Kyung-Min Yang or Seong-Jin Kim.
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.
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