Ferlin Overview: From Membrane to Cancer Biology

Cells. 2019 Aug 22;8(9):954. doi: 10.3390/cells8090954.

Abstract

In mammal myocytes, endothelial cells and inner ear cells, ferlins are proteins involved in membrane processes such as fusion, recycling, endo- and exocytosis. They harbour several C2 domains allowing their interaction with phospholipids. The expression of several Ferlin genes was described as altered in several tumoural tissues. Intriguingly, beyond a simple alteration, myoferlin, otoferlin and Fer1L4 expressions were negatively correlated with patient survival in some cancer types. Therefore, it can be assumed that membrane biology is of extreme importance for cell survival and signalling, making Ferlin proteins core machinery indispensable for cancer cell adaptation to hostile environments. The evidences suggest that myoferlin, when overexpressed, enhances cancer cell proliferation, migration and metabolism by affecting various aspects of membrane biology. Targeting myoferlin using pharmacological compounds, gene transfer technology, or interfering RNA is now considered as an emerging therapeutic strategy.

Keywords: C2 domain; dysferlin; ferlin; myoferlin; otoferlin; plasma membrane.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Membrane / metabolism*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / pathology

Substances

  • Calcium-Binding Proteins
  • MYOF protein, human
  • Membrane Proteins
  • Muscle Proteins
  • OTOF protein, human