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Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
Protein tyrosine phosphatase PTPRB regulates Src phosphorylation and tumour progression in NSCLC
Yinliang Qi1,2, Yuanchang Dai2, Shuyu Gui1
1Department of Respiratory Disease, Anhui Medical University, Hefei, Anhui, China.
Abstract:
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.
Insights
Protein tyrosine phosphatase receptor type B (PTPRB) suppresses non-small-cell lung cancer (NSCLC) growth and invasion. Down-regulation of PTPRB correlates with poor patient survival, suggesting its potential as a prognostic biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Protein tyrosine-phosphatases (PTPs) are crucial in cellular signaling and implicated in cancer.
- The specific role of protein tyrosine phosphatase receptor type B (PTPRB) in non-small-cell lung cancer (NSCLC) tumorigenesis remains uncharacterized.
Purpose of the Study:
- To investigate the function of PTPRB in NSCLC development and progression.
- To determine if PTPRB expression is associated with patient prognosis in NSCLC.
Main Methods:
- Utilized lentiviral vectors to overexpress or knockdown PTPRB in NSCLC cell lines (A549, H1299).
- Assessed cell proliferation, colony formation, soft agar growth, and invasion assays in vitro.
- Evaluated PTPRB's in vivo function using an A549 xenograft mouse model.
- Quantified PTPRB expression in NSCLC patient samples via quantitative PCR (qPCR).
- Performed Kaplan-Meier and multivariate analyses to correlate PTPRB expression with overall survival (OS).
Main Results:
- PTPRB overexpression inhibited NSCLC cell proliferation, colony formation, soft agar growth, and invasion.
- PTPRB knockdown enhanced Src phosphorylation and cell invasion, effects reversible by a Src inhibitor (PP2).
- PTPRB was found to be downregulated in NSCLC patient samples.
- Lower PTPRB expression was significantly associated with poorer patient overall survival.
Conclusions:
- PTPRB plays a tumor-suppressive role in NSCLC by regulating Src phosphorylation and inhibiting tumorigenesis.
- PTPRB expression level serves as an independent prognostic biomarker for NSCLC patients.
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