PLS3 predicts poor prognosis in pancreatic cancer and promotes cancer cell proliferation via PI3K/AKT signaling

J Cell Physiol. 2020 Nov;235(11):8416-8423. doi: 10.1002/jcp.29685. Epub 2020 Apr 2.

Abstract

Plastin-3 plays a key role in cancer cell proliferation and invasion, but its prognostic value in pancreatic cancer (PACA) remains poorly defined. In this study, we show that PLS3 messenger RNA is overexpressed in PACA tissue compared with normal tissue. We accumulated 207 cases of PACA specimens to perform immunohistochemical analysis and demonstrated that PLS3 levels correlate with T-classification (p < .001) and pathology (p < .001). Furthermore, overall survival rates (p < .001) in tumors with high PLS3 expression were poor, as assessed through Kaplan-Meier survival analysis. PLS3 was found to be an independent prognostic factor for PACA through multivariate Cox regression analysis. Moreover, we found that PLS3 enhances the proliferation and invasion of tumor cells as assessed through Cell Counting Kit-8, wounding healing assays, and Transwell assays. The upregulation of PLS3 also led to enhanced phosphatidylinositol-3 kinase/protein kinase B signaling in PACA cells. These data suggest that PLS3 is a biomarker to estimate PACA progression and represents a molecular target for PACA therapy.

Keywords: PI3K/AKT signaling pathway; PLS3; pancreatic cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism*
  • Neoplasm Invasiveness / genetics
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / genetics

Substances

  • Membrane Glycoproteins
  • Microfilament Proteins
  • plastin
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt