Plin2 inhibits autophagy via activating AKT/mTOR pathway in non-small cell lung cancer

Exp Cell Res. 2024 Feb 15;435(2):113955. doi: 10.1016/j.yexcr.2024.113955. Epub 2024 Jan 30.

Abstract

Perilipin 2 (Plin2) is known to be dysregulated in several human malignancies, which facilitates cancer progression. Recent studies have found that the abnormal expression of Plin2 is associated with poor prognosis of non-small cell lung cancer (NSCLC). However, the specific role of Plin2 and its underlying mechanism remain unclear. This study revealed that Plin2 expression was low in NSCLC tissues, and its relatively higher expression indicated larger tumor size and poorer prognosis. In vitro experiments proved that Plin2 promoted NSCLC cellular proliferation and inhibited autophagy by activating the AKT/mTOR pathway. Meanwhile, treatment with the AKT phosphorylation promoter or inhibitor neutralized the influence of Plin2 depletion or over-expression on proliferation and autophagy, respectively. In vivo study showed that Plin2 stimulated subcutaneous tumorigenesis of NSCLC cells in nude mice. Collectively, this study clarified the carcinogenic role of Plin2 and its molecular mechanism in NSCLC progression, which may facilitate a targeted therapy in the future.

Keywords: AKT; Autophagy; NSCLC; Plin2; mTOR.

MeSH terms

  • Animals
  • Autophagy / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Lung Neoplasms* / pathology
  • Mice
  • Mice, Nude
  • Perilipin-2 / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Perilipin-2
  • TOR Serine-Threonine Kinases