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Updated: May 16, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
TCPTP regulates SFK and STAT3 signaling and is lost in triple-negative breast cancers
Benjamin J Shields1, Florian Wiede, Esteban N Gurzov
1Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
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.
Insights
Decreased protein tyrosine phosphatase TCPTP (PTPN2) is linked to aggressive breast cancer. Restoring TCPTP inhibits cancer cell growth and tumor development, highlighting its tumor suppressor role.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tyrosine phosphorylation signaling pathways, including those involving epidermal growth factor receptor (EGFR) family, Src family kinases (SFKs), and signal transducer and activator of transcription 3 (STAT3), are crucial in human breast cancer development.
- These signaling molecules can be regulated by the protein tyrosine phosphatase TCPTP (PTPN2).
Purpose of the Study:
- To investigate the role of TCPTP (PTPN2) in human breast cancer.
- To determine if TCPTP functions as a tumor suppressor in breast cancer.
Main Methods:
- Analysis of TCPTP protein levels in breast cancer cell lines and primary tumors.
- Assessment of SFK and STAT3 signaling in TCPTP-deficient murine mammary fat pads and human breast cancer cell lines.
- Evaluation of TCPTP reconstitution effects on cancer cell proliferation, anchorage-independent growth, and xenograft tumor growth.
Main Results:
- TCPTP protein levels are reduced in a subset of breast cancer cell lines and absent in many triple-negative breast cancers.
- TCPTP deficiency correlates with increased SFK and STAT3 signaling in both murine and human models.
- Reconstitution of TCPTP significantly inhibited breast cancer cell proliferation, anchorage-independent growth, and xenograft tumor growth.
Conclusions:
- TCPTP deficiency contributes to enhanced pro-cancer signaling pathways in breast cancer.
- TCPTP acts as a tumor suppressor in human breast cancer, with potential therapeutic implications.
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