The Nonreceptor-Type Tyrosine Phosphatase PTPN13 Is a Tumor Suppressor Gene in Non–Small Cell Lung Cancer

Abstract

The aim of the present work was to identify protein tyrosine phosphatases (PTPs) as novel, candidate tumor suppressor genes in lung cancer. Among the 38 PTPs in the human genome that show specificity for phosphotyrosine, we identified six PTPs by quantitative RT-PCR whose mRNA expression levels were significantly down-regulated in lung cancer-derived cell lines (ie, PTPRE, PTPRF, PTPRU, PTPRK, PTPRD, and PTPN13). After validation in primary samples of non-small cell lung cancer (NSCLC), we selected PTPN13 for further studies. The results presented here demonstrate that PTPN13 is a candidate tumor suppressor gene that is frequently inactivated in NSCLC through the loss of either mRNA and protein expression (64/87, 73%) or somatic mutation (approximately 8%). Loss of PTPN13 expression was apparently due to the loss of one or both copies of the PTPN13 locus at 4q (approximately 26% double deletion and approximately 37% single deletion) but not to promoter methylation. Finally, the manipulation of PTPN13 expression in lung cancer cells (ie, NCI-H292, A549) demonstrated that PTPN13 negatively regulates anchorage-dependent and anchorage-independent growth in vitro and restrains tumorigenicity in vivo, possibly through the control of the tyrosine phosphorylation of both EGFR and HER2. In conclusion, the expression screening of PTPs in lung cancer reported here has identified PTPN13 as a novel candidate tumor suppressor in NSCLC whose loss increases signaling from epidermal growth factor receptor and HER2 tyrosine kinase receptors.

Conserved recurrent gene mutations correlate with pathway deregulation and clinical outcomes of lung adenocarcinoma in never-smokers

“…In addition to the commonly mutated genes such as EGFR, KRAS, and TP53 , we found several genes not reported before and all involved in tumor biology. PTPN13 a tumor suppressor is often inactivated in non-small cell lung cancer due to the loss of either mRNA and protein expression or somatic mutation [23,24]. In this set of tumors, all from never smokers, we did not see the significant differential expression compared to their paired normal lung.…”

miR-26a desensitizes non-small cell lung cancer cells to tyrosine kinase inhibitors by targeting PTPN13

“…In line with its oncogenic role during pulmonary tumorigenesis, we established here that miR-26a also targets PTPN13 to promote cell growth and EGFR-TKI resistance of NSCLC cells. The nonreceptor-type tyrosine phosphatase PTPN13 is reported as a tumor suppressor gene in NSCLCs [50]. It is frequently inactivated in NSCLC through the loss of either mRNA and protein expression or somatic mutation [50].…”

“…The nonreceptor-type tyrosine phosphatase PTPN13 is reported as a tumor suppressor gene in NSCLCs [50]. It is frequently inactivated in NSCLC through the loss of either mRNA and protein expression or somatic mutation [50]. The loss of PTPN13 increases signaling from EGFR and HER2 [50].…”

Tumor-suppressive Function of Protein-tyrosine Phosphatase Non-receptor Type 23 in Testicular Germ Cell Tumors Is Lost upon Overexpression of miR142–3p microRNA

“…PTPN23 (or His domain-containing protein-tyrosine phosphatase) belongs to the non-receptor class subfamily of the PTP family, several members of which have been implicated in tumor suppression (2). For example, loss of PTPN13 in non-small-cell lung cancer was shown to be associated with increased signaling through the epidermal growth factor receptor and HER2 tyrosine kinase receptors (3).…”