Overexpression of PTPRN Promotes Metastasis of Lung Adenocarcinoma and Suppresses NK Cell Cytotoxicity

Background Lung adenocarcinoma (LUAD) is the most common diagnostic histologic subtype of non-small cell lung cancer, but the role of receptor-type tyrosine-protein phosphatase-like N (PTPRN) in LUAD has not been studied. Methods We conducted a bioinformatic analysis to identify the expression of PTPRN on LUAD data from the Cancer Genome Atlas (TCGA) and the relationship between PTPRN and overall survival of LUAD patients. The effects of PTPRN on the migration ability of LUAD cells and the underlying mechanisms were investigated by in vitro and in vivo assays (i.e., wound healing assay, transwell assay, western blotting, xenograft model, and immunohistochemistry). Gene-set enrichment analysis and computational resource were used to analyze the correlation between PTPRN and different tumor-infiltrating immune cells (TIICs). Lactate dehydrogenase assay and Enzyme-linked immunosorbent assay were conducted to examine natural killer (NK) cell cytotoxicity. Results In our study, we found that PTPRN was up-regulated in LUAD and related to metastasis of LUAD patients. Besides, PTPRN was correlated with poor prognosis in the TCGA-LUAD dataset. PTPRN overexpression promoted LUAD cell migration and the expression of EMT markers by influencing MEK/ERK and PI3K/AKT signaling. Moreover, PTPRN expression was significantly associated with TIICs, especially NK cells. A549 and H1299 cells overexpressed PTPRN inhibited NK cell cytotoxicity. Conclusion Taken together, these findings demonstrated that PTPRN might be a potential and novel therapeutic target modulating antitumor immune response in treatment of LUAD.

Automated summary

The study found that PTPRN was up-regulated in LUAD and correlated with metastasis and poor prognosis of LUAD patients. PTPRN overexpression promoted LUAD cell migration, influenced MEK/ERK and PI3K/AKT signaling, and inhibited NK cell cytotoxicity. PTPRN may serve as a potential therapeutic target for modulating antitumor immune response in the treatment of LUAD.