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Updated: Jun 20, 2026

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The extracellular loop 2 of TM4SF5 inhibits integrin alpha2 on hepatocytes under collagen type I environment

Sin-Ae Lee1, Young Mee Kim, Tae Kyoung Kwak

  • 1Cancer Research Institute, College of Medicine, Cell Dynamics Research Center, Seoul, Korea.

Carcinogenesis
|October 1, 2009
PubMed

Insights

Transmembrane 4 L6 family member 5 (TM4SF5) inhibits cell spreading and migration on collagen I by interacting with integrin alpha2. Suppressing TM4SF5 restores normal cell functions, highlighting its role in regulating cell movement.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The transmembrane 4 superfamily (TM4SF) includes proteins involved in cell migration.
  • Four-transmembrane L6 family member 5 (TM4SF5) is implicated in uncontrolled cell proliferation and angiogenesis.
  • The specific roles of TM4SF5 in cell spreading and migration remain largely uncharacterized.

Purpose of the Study:

  • To investigate the function of TM4SF5 in hepatocarcinoma cell spreading and migration.
  • To elucidate the interaction between TM4SF5 and integrins in a collagen I environment.

Main Methods:

  • Utilized hepatocarcinoma cell clones with ectopic TM4SF5 expression.
  • Investigated extracellular interactions between TM4SF5 and integrin alpha2.
  • Assessed cell spreading and migration on collagen type I.
  • Employed TM4SF5 suppression and peptide/mutagenesis to disturb TM4SF5 structure.

Main Results:

  • Extracellular interaction between TM4SF5 and integrin alpha2 inhibited integrin alpha2-mediated cell spreading and migration on collagen I.
  • Suppression of TM4SF5 expression restored normal cell spreading and migration.
  • Structural disturbance of TM4SF5's second extracellular loop also recovered integrin alpha2 functions.

Conclusions:

  • TM4SF5 negatively regulates integrin alpha2 function in hepatocytes.
  • This regulation occurs through an interaction between TM4SF5's extracellular loop 2 and integrin alpha2.
  • These findings are relevant to cell spreading and migration in collagen I-rich environments.

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