Frontiers in Cell and Developmental Biology (Jun 2021)

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

  • Xinyue Song,
  • Xinyue Song,
  • Xinyue Song,
  • Xinyue Song,
  • Xue Jiao,
  • Xue Jiao,
  • Xue Jiao,
  • Xue Jiao,
  • Han Yan,
  • Han Yan,
  • Han Yan,
  • Han Yan,
  • Lifeng Yu,
  • Lifeng Yu,
  • Lifeng Yu,
  • Lifeng Yu,
  • Longyang Jiang,
  • Longyang Jiang,
  • Longyang Jiang,
  • Longyang Jiang,
  • Ming Zhang,
  • Ming Zhang,
  • Ming Zhang,
  • Ming Zhang,
  • Lianze Chen,
  • Lianze Chen,
  • Lianze Chen,
  • Lianze Chen,
  • Mingyi Ju,
  • Mingyi Ju,
  • Mingyi Ju,
  • Mingyi Ju,
  • Lin Wang,
  • Lin Wang,
  • Lin Wang,
  • Lin Wang,
  • Qian Wei,
  • Qian Wei,
  • Qian Wei,
  • Qian Wei,
  • Lin Zhao,
  • Lin Zhao,
  • Lin Zhao,
  • Lin Zhao,
  • Minjie Wei,
  • Minjie Wei

DOI
https://doi.org/10.3389/fcell.2021.622018
Journal volume & issue
Vol. 9

Abstract

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BackgroundLung 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.MethodsWe 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.ResultsIn 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.ConclusionTaken together, these findings demonstrated that PTPRN might be a potential and novel therapeutic target modulating antitumor immune response in treatment of LUAD.

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