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RhoA-dependent regulation of cell migration by the tumor suppressor hSNF5/INI1

Julie Caramel1, Frédérique Quignon, Olivier Delattre

  • 1Institut Curie and Institut National de la Santé et de la Recherche Medicale U830, Unité de Génétique et Biologie des Cancers, Paris, France.

Cancer Research
|August 5, 2008
PubMed

Insights

Loss of the hSNF5/INI1 tumor suppressor impairs cell migration in pediatric cancers. Restoring hSNF5/INI1 function inhibits migration by regulating RhoA activity, crucial for preventing tumor invasion.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Malignant rhabdoid tumors (MRTs) are aggressive pediatric cancers linked to hSNF5/INI1 inactivation.
  • hSNF5/INI1 is a core component of the SWI/SNF chromatin remodeling complex, involved in cell cycle and differentiation.
  • MRTs exhibit high invasiveness, suggesting a role for hSNF5/INI1 in cell migration.

Purpose of the Study:

  • To investigate the role of hSNF5/INI1 in regulating cell migration.
  • To elucidate the molecular mechanisms by which hSNF5/INI1 influences cell movement.
  • To determine if impaired hSNF5/INI1 function contributes to MRT invasiveness.

Main Methods:

  • Utilized MRT cell lines with varying hSNF5/INI1 expression levels.
  • Performed gene knockdown experiments in epithelial cell lines (293T, MCF7).
  • Analyzed actin cytoskeleton organization, RhoA GTPase activity, and cell migration assays.

Main Results:

  • hSNF5/INI1 expression reduced migration in MRT cells, linked to actin disorganization.
  • Loss of hSNF5/INI1 increased cell size, reduced cell adhesion, and enhanced migration in epithelial cells.
  • Mechanism involves SWI/SNF-dependent transcriptional inhibition of RhoA activity.
  • SNF5 homology domain and specific mutations (S284L) impact hSNF5/INI1's migratory function.

Conclusions:

  • hSNF5/INI1 functions as a tumor suppressor by inhibiting cell migration.
  • Loss of hSNF5/INI1 contributes to the high invasiveness and metastatic potential of MRTs.
  • Targeting hSNF5/INI1 pathways may offer therapeutic strategies for aggressive pediatric tumors.

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