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Syndecan-2 enhances invasive motility in colon cancer cells via a laminin-332-integrin α6β1 axis

Subin Cho1, Jisun Hwang1, Eunhye Park1

  • 1Department of Life Sciences, Ewha Womans University, Seoul, South Korea.

The Journal of Biological Chemistry
|August 17, 2026
PubMed

Insights

Syndecan-2 (SDC-2) enhances colon cancer cell motility by interacting with laminin-332 and integrin α6β1. This SDC-2-laminin-332-integrin axis promotes cell adhesion and migration, offering a potential therapeutic target.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Extracellular Matrix Biology

Background:

  • Syndecan-2 (SDC-2) is implicated in colon cancer progression.
  • Its precise role in cell motility, particularly its interaction with integrins, requires further elucidation.

Purpose of the Study:

  • To investigate the functional cooperation between SDC-2 and integrins in colon cancer cell migration.
  • To identify the specific extracellular matrix components involved in this interaction.

Main Methods:

  • Overexpression of SDC-2 in HT29 colon cancer cells.
  • Assessment of cell adhesion, spreading, and migration on laminin-332.
  • Analysis of integrin localization and expression of laminin-332 subunits.
  • Proximity ligation assays to detect SDC-2 and integrin interactions.
  • Inhibition studies using anti-integrin α6 antibody and laminin-α3 peptide.

Main Results:

  • SDC-2 overexpression enhanced HT29 cell adhesion, spreading, and migration on laminin-332.
  • This correlated with increased basal membrane localization of integrin α6 and elevated laminin-332 expression and deposition.
  • Enhanced interactions between SDC-2 and integrin α6β1 were observed.
  • Adhesion was dependent on specific laminin-332 modules and inhibited by targeting integrin α6 or laminin-α3.
  • Combined antibody and peptide treatment suppressed migration and invasion in metastatic DLD-1 cells.

Conclusions:

  • A novel SDC-2-laminin-332-integrin α6β1 signaling axis drives invasive motility in colorectal cancer.
  • This axis represents a potential therapeutic target for metastatic colorectal cancer.
Keywords:
adhesioncancerextracellular matrixintegrinlaminin-332syndecan-2

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