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

doi:10.1038/s41467-019-13852-5

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

Department of Surgery

Research output: Contribution to journal › Article › peer-review

20 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 language	English
Article number	5805
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13852-5
Publication status	Published - 2019 Dec 1

Bibliographical note

Funding Information:
This work was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (HA17C0037). K.-M.Y is the recipient of a National Research Foundation grant of Korea (NRF-2017R1D1A1B0 3035390) funded by the Ministry of Education.

Publisher Copyright:
© 2019, The Author(s).

All Science Journal Classification (ASJC) codes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-019-13852-5

Cite this

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

@article{75ed5b7fff7f40ea8132d9772298116d,

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

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.",

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

note = "Funding Information: This work was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (HA17C0037). K.-M.Y is the recipient of a National Research Foundation grant of Korea (NRF-2017R1D1A1B0 3035390) funded by the Ministry of Education. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-019-13852-5",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - RNF208, an estrogen-inducible E3 ligase, targets soluble Vimentin to suppress metastasis in triple-negative breast cancers

AU - Pang, Kyoungwha

AU - Park, Jinah

AU - Ahn, Sung Gwe

AU - Lee, Jihee

AU - Park, Yuna

AU - Ooshima, Akira

AU - Mizuno, Seiya

AU - Yamashita, Satoshi

AU - Park, Kyung Soon

AU - Lee, So Young

AU - Jeong, Joon

AU - Ushijima, Toshikazu

AU - Yang, Kyung Min

AU - Kim, Seong Jin

N1 - Funding Information: This work was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (HA17C0037). K.-M.Y is the recipient of a National Research Foundation grant of Korea (NRF-2017R1D1A1B0 3035390) funded by the Ministry of Education. Publisher Copyright: © 2019, The Author(s).

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85076887712&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076887712&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-13852-5

DO - 10.1038/s41467-019-13852-5

M3 - Article

C2 - 31862882

AN - SCOPUS:85076887712

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5805

ER -

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this