title: Protein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis.
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.
authors.affiliation: Cancer Biology and Pharmacology, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672.
authors.forename: Shuet Theng
authors.initials: ST
authors.lastname: Lee
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.forename: Yong
authors.initials: Y
authors.lastname: Wei
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Li
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Qiao
authors.forename: Peiyong
authors.initials: P
authors.lastname: Guan
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.forename: Chew Hooi
authors.initials: CH
authors.lastname: Wong
authors.forename: Kelly
authors.initials: K
authors.lastname: Huynh
authors.forename: Jinhua
authors.initials: J
authors.lastname: Wang
authors.forename: Juntao
authors.initials: J
authors.lastname: Li
authors.forename: K Murthy
authors.initials: KM
authors.lastname: Karuturi
authors.forename: Ern Yu
authors.initials: EY
authors.lastname: Tan
authors.forename: Dave S B
authors.initials: DS
authors.lastname: Hoon
authors.forename: Yibin
authors.initials: Y
authors.lastname: Kang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yu
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D017027:Protein Tyrosine Phosphatases; C489397:UBASH3B protein, human