Protein tyrosine phosphatase PTPRB regulates Src phosphorylation and tumour progression in NSCLC.
Protein tyrosine-phosphatases (PTPs) play important roles in various biological processes. Deregulation in PTP function has been implicated in carcinogenesis and tumour progression in many cancer types. However, the role of protein tyrosine phosphatase receptor type B (PTPRB) in non-small-cell lung cancer (NSCLC) tumorigenesis has not been investigated. Lentiviral vector expressing PTPRB cDNA or shRNA was infected into A549 and H1299 cell lines, followed by cell proliferation, colony formation, soft agar and invasion assays. A549 xenograft mouse model was used to evaluate in vivo function of PTPRB. Quantitative polymerase chain reaction (PCR) was used to measure PTPRB expression in NSCLC patient samples. Kaplan Meier analysis was performed to assess association between PTPRB expression and patient overall survival (OS). Multivariate analysis was performed to evaluate prognostic significance of PTPRB. Overexpression of PTPRB reduced cell proliferation rate, colony formation efficiency, soft agar growth and cell invasion in A549 and H1299 cells, as well as tumour growth rate in A549 xenograft. Knockdown of PTPRB increased Src phosphorylation and cell invasion, which was reversed by Src inhibitor PP2. Additionally, PTPRB was down-regulated in NSCLC patient and was associated with patient OS. PTPRB regulates Src phosphorylation and tumorigenesis in NSCLC. PTPRB may serve as an independent prognostic biomarker for NSCLC patients.
Department of Respiratory Disease, Anhui Medical University, Hefei, Anhui, China.|General Department of Hyperbaric Oxygen, The Second People's Hospital of Hefei, Hefei, Anhui, China.
Yinliang
Y
Qi
General Department of Hyperbaric Oxygen, The Second People's Hospital of Hefei, Hefei, Anhui, China.
Yuanchang
Y
Dai
Department of Respiratory Disease, Anhui Medical University, Hefei, Anhui, China.
Shuyu
S
Gui
D000072283:A549 Cells; D000328:Adult; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000502:physiology*; D015996:Survival Rate / Q000639:trends; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D015688:Oncogene Protein pp60(v-src); C516886:PTPRB protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3
NSCLC; PTPRB; prognostic biomarker; tumour progression