Tumor Biology

, Volume 37, Issue 10, pp 13479–13487 | Cite as

PTP1B promotes aggressiveness of breast cancer cells by regulating PTEN but not EMT

  • Xue Liu
  • Qian Chen
  • Xu-Gang Hu
  • Xian-Chao Zhang
  • Ti-Wei Fu
  • Qing Liu
  • Yan Liang
  • Xi-Long Zhao
  • Xia Zhang
  • Yi-Fang Ping
  • Xiu-Wu Bian
Original Article

Abstract

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.

Keywords

Breast cancer PTP1B PTEN MMPS Invasion 

Notes

Acknowledgments

This project was supported by grants from the National Natural Science Foundation of China (no. 81230062).

Authors’ contributions

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

None

Supplementary material

13277_2016_5245_MOESM1_ESM.docx (17 kb)
ESM 1 Supplementary Table 1 Antibodies used in this study. Supplementary Table 2 Primers used in this study. (DOCX 16 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Xue Liu
    • 1
  • Qian Chen
    • 1
  • Xu-Gang Hu
    • 1
  • Xian-Chao Zhang
    • 1
  • Ti-Wei Fu
    • 1
  • Qing Liu
    • 1
  • Yan Liang
    • 1
  • Xi-Long Zhao
    • 1
  • Xia Zhang
    • 1
  • Yi-Fang Ping
    • 1
  • Xiu-Wu Bian
    • 1
  1. 1.Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of ChinaChongqingChina

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