Role of fibroblast growth factor receptor-2 splicing in normal and cancer cells

Front Biosci (Landmark Ed). 2018 Jan 1;23:626-639. doi: 10.2741/4609.

Abstract

Types 1-4 of fibroblast growth factor receptors (FGFR) are all expressed in various cancers. Because of its prominent role in carcinogenesis and cancer progression, FGFR-2, is being considered as a novel target in cancer treatment. Owing to the alternative splicing of its extracellular domain, FGFR-2 exists in two variants: IIIb and IIIc. FGFR-2 IIIb is mainly expressed in normal epithelial cells, as well as in oral mucosal, esophageal, gastric, colorectal, pancreatic, pulmonary, breast, endometrial, cervical, and prostate cancers. The IIIc variant of FGFR is expressed in mesenchymal cells, and during epithelial-mesenchymal transition (EMT), is expressed in colorectal, pancreatic, bladder, cervical, and prostate cancers. The FGFR IIIb and IIIc variants bind different forms of FGFs and exert autocrine and/or paracrine effects in cancers. Recent reports indicate that switching from IIIb to IIIc variants correlates with the aggressiveness of the cancers via EMT. Here, we discuss the expression, role, and regulatory mechanisms of IIIb and IIIc variants of FGFR in cancers.

Publication types

  • Review

MeSH terms

  • Alternative Splicing*
  • Benzamides / therapeutic use
  • Epithelial Cells / metabolism*
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Piperazines / therapeutic use
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Pyrazoles / therapeutic use
  • Receptor, Fibroblast Growth Factor, Type 2 / antagonists & inhibitors
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism

Substances

  • AZD4547
  • Benzamides
  • Piperazines
  • Protein Isoforms
  • Pyrazoles
  • Receptor, Fibroblast Growth Factor, Type 2