title: PTP1B promotes aggressiveness of breast cancer cells by regulating PTEN but not EMT.
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.
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.
authors.forename: Xu-Gang
authors.initials: XG
authors.lastname: Hu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.
authors.forename: Xian-Chao
authors.initials: XC
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.
authors.forename: Ti-Wei
authors.initials: TW
authors.lastname: Fu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zhao
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China. pingyifang@126.com.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Ping
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China. bianxiuwu@263.net.
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Breast cancer; Invasion; MMPS; PTEN; PTP1B