Cell Cycle Progression Regulates Biogenesis and Cellular Localization of Lipid Droplets

Mol Cell Biol. 2019 Apr 16;39(9):e00374-18. doi: 10.1128/MCB.00374-18. Print 2019 May 1.

Abstract

Intracellular lipid accumulation has been associated with a poor prognosis in cancer. We have previously reported the involvement of lipid droplets in cell proliferation in colon cancer cells, suggesting a role for these organelles in cancer development. In this study, we evaluate the role of lipid droplets in cell cycle regulation and cellular transformation. Cell cycle synchronization of NIH 3T3 cells revealed increased numbers and dispersed distribution of lipid droplets specifically during S phase. Also, the transformed cell lineage NIH 3T3-H-rasV12 showed an accumulation of both lipid droplets and PLIN2 protein above the levels in NIH 3T3 cells. PLIN2 gene overexpression, however, was not able to induce NIH 3T3 cell transformation, disproving the hypothesis that PLIN2 is an oncogene. Furthermore, positive PLIN2 staining was strongly associated with highly proliferative Ki-67-positive areas in human colon adenocarcinoma tissue samples. Taken together, these results indicate that cell cycle progression is associated with tight regulation of lipid droplets, a process that is altered in transformed cells, suggesting the existence of a mechanism that connects cell cycle progression and cell proliferation with lipid accumulation.

Keywords: PLIN2; cell cycle; cellular transformation; lipid droplets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Cycle
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lipid Droplets / metabolism*
  • Mice
  • NIH 3T3 Cells
  • Perilipin-2 / genetics
  • Perilipin-2 / metabolism*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • PLIN2 protein, human
  • Perilipin-2
  • Plin2 protein, mouse
  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)