TCPTP regulates SFK and STAT3 signaling and is lost in triple-negative breast cancers.

Abstract:

:Tyrosine phosphorylation-dependent signaling, as mediated by members of the epidermal growth factor receptor (EGFR) family (ErbB1 to -4) of protein tyrosine kinases (PTKs), Src family PTKs (SFKs), and cytokines such as interleukin-6 (IL-6) that signal via signal transducer and activator of transcription 3 (STAT3), is critical to the development and progression of many human breast cancers. EGFR, SFKs, and STAT3 can serve as substrates for the protein tyrosine phosphatase TCPTP (PTPN2). Here we report that TCPTP protein levels are decreased in a subset of breast cancer cell lines in vitro and that TCPTP protein is absent in a large proportion of "triple-negative" primary human breast cancers. Homozygous TCPTP deficiency in murine mammary fat pads in vivo is associated with elevated SFK and STAT3 signaling, whereas TCPTP deficiency in human breast cancer cell lines enhances SFK and STAT3 signaling. On the other hand, TCPTP reconstitution in human breast cancer cell lines severely impaired cell proliferation and suppressed anchorage-independent growth in vitro and xenograft growth in vivo. These studies establish TCPTP's potential to serve as a tumor suppressor in human breast cancer.

journal_name

Mol Cell Biol

authors

Shields BJ,Wiede F,Gurzov EN,Wee K,Hauser C,Zhu HJ,Molloy TJ,O'Toole SA,Daly RJ,Sutherland RL,Mitchell CA,McLean CA,Tiganis T

doi

10.1128/MCB.01016-12

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

557-70

issue

3

eissn

0270-7306

issn

1098-5549

pii

MCB.01016-12

journal_volume

33

pub_type

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