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CD98hc (SLC3A2) mediates integrin signaling

Chloe C Feral1, Naoyuki Nishiya, Csilla A Fenczik

  • 1Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 31, 2004
PubMed

Insights

CD98hc protein is crucial for integrin signaling, promoting cell migration, survival, and tumor growth. Its interaction with integrins, independent of amino acid transport, drives tumorigenesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Integrins are key regulators of cellular functions via signaling pathways.
  • CD98 heterodimers, including CD98hc (SLC3A2), interact with integrins.
  • CD98hc overexpression is linked to cell growth and tumorigenesis.

Purpose of the Study:

  • To elucidate the biological role of CD98hc by analyzing CD98hc-null cells.
  • To determine CD98hc's contribution to integrin-dependent signaling and cellular behaviors.
  • To investigate CD98hc's role in tumorigenesis.

Main Methods:

  • Gene disruption to create CD98hc-null cells.
  • Analysis of cell spreading, migration, and apoptosis in CD98hc-null cells.
  • Assessment of Akt and Rac GTPase activation upon cell adhesion.
  • Utilizing a CD98hc mutant to differentiate integrin interaction from amino acid transport.

Main Results:

  • CD98hc is essential for integrin-dependent cell spreading, migration, and apoptosis resistance.
  • CD98hc mediates adhesion-induced activation of Akt and Rac GTPase.
  • A CD98hc mutant interacting with beta1 integrins, but not light chains, rescued signaling and survival.
  • CD98hc deletion impaired teratocarcinoma formation in mice, which was restorable by CD98hc or the integrin-binding mutant.

Conclusions:

  • CD98hc functions as an integrin-associated protein mediating critical integrin-dependent signals.
  • These signals, including those regulating cell survival and migration, are vital for tumorigenesis.
  • CD98hc's role in integrin signaling, rather than amino acid transport, is key to its pro-tumorigenic function.

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