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TCPTP regulates SFK and STAT3 signaling and is lost in triple-negative breast cancers.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2013 Feb; Vol. 33 (3), pp. 557-70. Date of Electronic Publication: 2012 Nov 19. - Publication Year :
- 2013
-
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.
- Subjects :
- Animals
Breast metabolism
Breast pathology
Breast Neoplasms genetics
Breast Neoplasms pathology
Cell Line, Tumor
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Mice
Mice, Inbred C57BL
Protein Tyrosine Phosphatase, Non-Receptor Type 2 genetics
Signal Transduction
Breast Neoplasms metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 2 metabolism
STAT3 Transcription Factor metabolism
src-Family Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 33
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 23166300
- Full Text :
- https://doi.org/10.1128/MCB.01016-12