Statins affect cancer cell plasticity with distinct consequences for tumor progression and metastasis

Cell Rep. 2021 Nov 23;37(8):110056. doi: 10.1016/j.celrep.2021.110056.

Abstract

Statins are among the most commonly prescribed drugs, and around every fourth person above the age of 40 is on statin medication. Therefore, it is of utmost clinical importance to understand the effect of statins on cancer cell plasticity and its consequences to not only patients with cancer but also patients who are on statins. Here, we find that statins induce a partial epithelial-to-mesenchymal transition (EMT) phenotype in cancer cells of solid tumors. Using a comprehensive STRING network analysis of transcriptome, proteome, and phosphoproteome data combined with multiple mechanistic in vitro and functional in vivo analyses, we demonstrate that statins reduce cellular plasticity by enforcing a mesenchymal-like cell state that increases metastatic seeding ability on one side but reduces the formation of (secondary) tumors on the other due to heterogeneous treatment responses. Taken together, we provide a thorough mechanistic overview of the consequences of statin use for each step of cancer development, progression, and metastasis.

Keywords: barcode screening; cellular plasticity; cholesterol pathway; mesenchymal cell state shift; statins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Plasticity / drug effects*
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Neoplasm Metastasis
  • Neoplasms / metabolism*
  • Neoplastic Stem Cells / pathology

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors