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

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... Full description

Journal Title: Proceedings of the National Academy of Sciences 02 July 2013, Vol.110(27), p.11121
Main Author: Shuet Theng Lee
Other Authors: 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
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1300873110
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recordid: pnas_s110_27_11121
title: Protein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis
format: Article
creator:
  • 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
subjects:
  • Sciences (General)
ispartof: Proceedings of the National Academy of Sciences, 02 July 2013, Vol.110(27), p.11121
description: 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.
language: eng
source:
identifier: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.1300873110
fulltext: fulltext_linktorsrc
issn:
  • 0027-8424
  • 00278424
  • 1091-6490
  • 10916490
url: Link


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titleProtein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis
creatorShuet 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
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descriptionEfforts 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.
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titleProtein tyrosine phosphatase UBASH3B is overexpressed in triple-negative breast cancer and promotes invasion and metastasis
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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.

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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.

pubNational Acad Sciences
doi10.1073/pnas.1300873110
urlhttp://www.pnas.org/content/110/27/11121.abstract
lad01Proceedings of the National Academy of Sciences
pages11121-11126
date2013-07-02