Please use this identifier to cite or link to this item: https://doi.org/10.1073/pnas.1300873110
Title: Protein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis
Authors: Lee, S.T.
Feng, M.
Wei, Y.
Li, Z.
Qiao, Y.
Guan, P.
Jiang, X.
Wong, C.H.
Huynh, K.
Wang, J.
Li, J.
Karuturi, K.M.
Tan, E.Y.
Hoon, D.S.B.
Kang, Y.
Yu, Q. 
Issue Date: 2-Jul-2013
Citation: Lee, S.T., Feng, M., Wei, Y., Li, Z., Qiao, Y., Guan, P., Jiang, X., Wong, C.H., Huynh, K., Wang, J., Li, J., Karuturi, K.M., Tan, E.Y., Hoon, D.S.B., Kang, Y., Yu, Q. (2013-07-02). Protein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis. Proceedings of the National Academy of Sciences of the United States of America 110 (27) : 11121-11126. ScholarBank@NUS Repository. https://doi.org/10.1073/pnas.1300873110
Abstract: Efforts to improve the clinical outcome of highly aggressive triple-negative breast cancer (TNBC) have been hindered by the lack of effective targeted therapies. Thus, it is important to identify the specific gene targets/pathways driving the invasive phenotype to develop more effective therapeutics. Here we show that ubiquitin-associated and SH3 domain-containing B (UBASH3B), a protein tyrosine phosphatase, is overexpressed in TNBC, where it supports malignant growth, invasion, and metastasis largely through modulating epidermal growth factor receptor (EGFR). We also show that UBASH3B is a functional target of anti-invasive microRNA200a (miR200a) that is down-regulated in TNBC. Importantly, the oncogenic potential of UBASH3B is dependent on its tyrosine phosphatase activity, which targets CBL ubiquitin ligase for dephosphorylation and inactivation, leading to EGFR up-regulation. Thus, UBASH3B may function as a crucial node in bridging multiple invasion-promoting pathways, thereby providing a potential therapeutic target for TNBC.
Source Title: Proceedings of the National Academy of Sciences of the United States of America
URI: http://scholarbank.nus.edu.sg/handle/10635/116543
ISSN: 00278424
DOI: 10.1073/pnas.1300873110
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