Protein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis
| Autor: | Ern Yu Tan, Zhe Li, Yuanyuan Qiao, K. M. Karuturi, Yibin Kang, S T Lee, Dave S.B. Hoon, Peiyong Guan, Qiang Yu, K. Huynh, Chee Howe Wong, J. Wang, Jun Li, Xia Jiang, Mengling Feng, Yunzhou Wei |
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| Rok vydání: | 2013 |
| Předmět: |
Transplantation
Heterologous Mice Nude Breast Neoplasms Protein tyrosine phosphatase Biology Metastasis Mice Downregulation and upregulation Cell Line Tumor microRNA medicine Animals Humans Neoplasm Invasiveness Epidermal growth factor receptor Neoplasm Metastasis Triple-negative breast cancer Mice Inbred BALB C Multidisciplinary Biological Sciences medicine.disease Up-Regulation Ubiquitin ligase Transplantation MicroRNAs Gene Knockdown Techniques biology.protein Cancer research Female Protein Tyrosine Phosphatases |
| Zdroj: | Proceedings of the National Academy of Sciences. 110:11121-11126 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1300873110 |
| Popis: | 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 microRNA 200a ( 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. |
| Databáze: | OpenAIRE |
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