PTP1B promotes aggressiveness of breast cancer cells by regulating PTEN but not EMT
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Metastasis is a complicated, multistep process and remains the major cause of cancer-related mortality. Exploring the molecular mechanisms underlying tumor metastasis is crucial for development of new strategies for cancer prevention and treatment. In this study, we found that protein tyrosine phosphatase 1B (PTP1B) promoted breast cancer metastasis by regulating phosphatase and tensin homolog (PTEN) but not epithelial-mesenchymal transition (EMT). By detecting PTP1B expression of the specimens from 128 breast cancer cases, we found that the level of PTP1B was higher in breast cancer tissues than the corresponding adjacent normal tissues. Notably, PTP1B was positively associated with lymph node metastasis (LNM) and estrogen receptor (ER) status. In vitro, disturbing PTP1B expression obviously attenuated cell migration and invasion. On the contrary, PTP1B overexpression significantly increased migration and invasion of breast cancer cells. Mechanistically, PTP1B knockdown upregulated PTEN, accompanied with an abatement of AKT phosphorylation and the expression of matrix metalloproteinase 2 (MMP2) and MMP7. Conversely, forced expression of PTP1B reduced PTEN and increased AKT phosphorylation as well as the expression of MMP2 and MMP7. Notably, neither EMT nor stemness of breast cancer cells was regulated by PTP1B. We also found that PTP1B acted as an independent prognostic factor and predicted poor prognosis in ER-positive breast cancer patients. Taken together, our findings provide advantageous evidence for the development of PTP1B as a potential therapeutic target for breast cancer, especially for ER-positive breast cancer patients.
KeywordsBreast cancer PTP1B PTEN MMPS Invasion
This project was supported by grants from the National Natural Science Foundation of China (no. 81230062).
Yi-Fang Ping, Xiu-Wu Bian, and Xue Liu designed the research; Xue Liu, Qian Chen, Xian-Chao Zhang, Ti-Wei Fu, and Qing Liu performed the experiments; Xue Liu, Xu-Gang Hu, Xi-Long Zhao, and Yan Liang analyzed experiment data; Xue Liu, Yi-Fang Ping, Xia Zhang, and Xiu-Wu Bian wrote the manuscript.
Compliance with ethical standards
Conflicts of interest
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