Important role of β1-integrin in fucoidan-induced apoptosis via caspase-8 activation

Yumi Yamasaki1, Masao Yamasaki, Hirofumi Tachibana

  • 1Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan. yamasakiy@cc.miyazaki-u.ac.jp

Insights

Fucoidan triggers breast cancer cell death by binding to β1-integrin, activating caspase-8. This interaction is crucial for fucoidan-induced apoptosis in MCF-7 cells.

Area of Science:

  • * Molecular Biology
  • * Cell Biology
  • * Cancer Research

Background:

  • * Fucoidan is known to induce apoptosis in human MCF-7 breast cancer cells via caspase-8 activation.
  • * The precise mechanism underlying fucoidan's apoptotic effect, particularly its cell surface interactions, remains unclear.

Purpose of the Study:

  • * To elucidate the mechanism of fucoidan-induced apoptosis in MCF-7 cells.
  • * To investigate the role of β1-integrin in fucoidan's interaction with the cell surface and subsequent apoptosis induction.

Main Methods:

  • * Investigated fucoidan's interaction with MCF-7 cell surface.
  • * Utilized gene silencing of β1-integrin to assess its role in apoptosis.
  • * Examined the formation of β1-integrin-caspase-8 complexes.
  • * Analyzed caspase-8 recruitment and cleavage associated with β1-integrin.

Main Results:

  • * Fucoidan binds to the cell surface, and β1-integrin is essential for this interaction.
  • * Silencing β1-integrin inhibited fucoidan-induced apoptosis and caspase-8 activation.
  • * Fucoidan promoted the formation of a β1-integrin-caspase-8 complex.
  • * Caspase-8 was recruited to and cleaved at the intracellular domain of β1-integrin, leading to its activation.

Conclusions:

  • * β1-integrin is a critical mediator for fucoidan cell-surface binding and subsequent apoptosis induction.
  • * Fucoidan activates apoptosis through a pathway involving β1-integrin and caspase-8 in MCF-7 cells.
  • * This study reveals a novel mechanism for fucoidan's anti-cancer effects in breast cancer cells.

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