Protein tyrosine phosphatase PTPRB regulates Src phosphorylation and tumour progression in NSCLC

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.

Upregulated miR‑665 expression independently predicts poor prognosis of lung cancer and facilitates tumor cell proliferation, migration and invasion

“…A study by Hu et al (33) demonstrated that miR-665 exerts promoting effects on hepatocellular carcinoma cell proliferation, migration and invasion by directly targeting PTPRB and through the Hippo signaling pathway. Interestingly, PTPRB has been found to suppress NSCLC cell proliferation and invasion by inhibiting the phosphorylation of the proto-oncogene tyrosine-protein kinase Src (36). In the present study, the binding site of miR-665 was predicted in the 3'-UTR of PTPRB, confirming that PTPRB was a direct target gene of miR-665 in NSCLC.…”

RETRACTED ARTICLE: miR-665 promotes hepatocellular carcinoma cell migration, invasion, and proliferation by decreasing Hippo signaling through targeting PTPRB

“…Targetscan and miRanda were used to analyze potential miR-665 targets. Among them, we were particularly interested in PTPRB, because the PTPR family is mostly regarded as tumor suppressors in carcinogenesis and cancer development 16 . RT-qPCR was used to analyze PTPRB expression in 50 paired HCC tissues and adjacent normal tissues.…”

“…Tyrosine phosphatase receptor type B (PTPRB) is a potential target of miR-665(predicted by TargetScan and miRanda). Recent studies have also discovered that PTPRB may function as a tumor suppressor in carcinogenesis and cancer development 16 . However, a functional link between the miR-665/PTPRB axis and Hippo signaling pathway in association with HCC proliferation, migration, and invasion remains to be further studied.…”

Identification of prognostic genes in adrenocortical carcinoma microenvironment based on bioinformatic methods

“…It was downregulated and was significantly associated with OS in NSCLC patients. Besides, PTPRB regulated the tumorigenesis and Scr phosphorylation . Weng et al reported that PTPRB promoted tumor metastasis and invasion of colorectal cancer via inducing epithelial mesenchymal transition.…”