Lipid metabolism reprogramming and its potential targets in cancer

Cancer Commun (Lond). 2018 May 21;38(1):27. doi: 10.1186/s40880-018-0301-4.

Abstract

Reprogramming of lipid metabolism is a newly recognized hallmark of malignancy. Increased lipid uptake, storage and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. Lipids constitute the basic structure of membranes and also function as signaling molecules and energy sources. Sterol regulatory element-binding proteins (SREBPs), a family of membrane-bound transcription factors in the endoplasmic reticulum, play a central role in the regulation of lipid metabolism. Recent studies have revealed that SREBPs are highly up-regulated in various cancers and promote tumor growth. SREBP cleavage-activating protein is a key transporter in the trafficking and activation of SREBPs as well as a critical glucose sensor, thus linking glucose metabolism and de novo lipid synthesis. Targeting altered lipid metabolic pathways has become a promising anti-cancer strategy. This review summarizes recent progress in our understanding of lipid metabolism regulation in malignancy, and highlights potential molecular targets and their inhibitors for cancer treatment.

Keywords: Cancer; Cholesterol; Fatty acids; Lipid droplets; Lipid metabolism; SCAP; SREBPs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Endoplasmic Reticulum / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lipid Metabolism / drug effects*
  • Lipogenesis / drug effects
  • Membrane Proteins / metabolism
  • Models, Biological
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Sterol Regulatory Element Binding Proteins / metabolism

Substances

  • Antineoplastic Agents
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • SREBP cleavage-activating protein
  • Sterol Regulatory Element Binding Proteins