LDL cholesterol promotes the proliferation of prostate and pancreatic cancer cells by activating the STAT3 pathway

J Cell Physiol. 2021 Jul;236(7):5253-5264. doi: 10.1002/jcp.30229. Epub 2020 Dec 23.

Abstract

Hypercholesterolemia has been found to be closely linked with a significant increase in both cancer incidence and mortality. However, the exact correlation between serum cholesterol levels and cancer has not been completely deciphered. Here we analyzed the effect of low-density lipoprotein (LDL) cholesterol on prostate and pancreatic cancer cells. We noted that LDL induced a substantial STAT3 activation and JAK1, JAK2, Src activation in diverse prostate and pancreatic tumor cells. Moreover, LDL promoted cancer cell proliferation, migration, and invasion as well as upregulated the expression of diverse oncogenic gene products. However, deletion of LDL-activated STAT3 in LNCaP and PANC-1 cells and reduced LDL-induced cell viability. Simvastatin (SV) treatment also alleviated LDL-induced cell viability and migration ability in both the prostate and pancreatic tumor cells. These results demonstrate that LDL-induced STAT3 activation may exert a profound effect on the proliferation and survival of tumor cells.

Keywords: STAT3; invasion; low-density lipoprotein cholesterol; pancreatic cancer; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / pharmacology
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Cell Survival / physiology
  • Cholesterol, LDL / metabolism*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Janus Kinase 1 / metabolism
  • Janus Kinase 2 / metabolism
  • Male
  • Pancreas / cytology
  • Pancreas / growth & development
  • Pancreas / pathology
  • Pancreatic Neoplasms / pathology*
  • Prostate / cytology
  • Prostate / growth & development
  • Prostate / pathology
  • Prostatic Neoplasms / pathology*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / physiology
  • Simvastatin / pharmacology

Substances

  • Anticholesteremic Agents
  • Cholesterol, LDL
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Simvastatin
  • JAK1 protein, human
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2