Protein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis

Shuet Theng Lee, Min Feng, Yong Wei, Zhimei Li, Yuanyuan Qiao, Peiyong Guan, Xia Jiang, Chew Hooi Wong, Kelly Huynh, Jinhua Wang, Juntao Li, K. Murthy Karuturi, Ern Yu Tan, Dave S.B. Hoon, Yibin Kang, Qiang Yu

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)11121-11126
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number27
DOIs
StatePublished - Jul 2 2013

All Science Journal Classification (ASJC) codes

  • General

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