Targeting Focal Adhesion Kinase Suppresses the Malignant Phenotype in Rhabdomyosarcoma Cells

Alicia M Waters1, Laura L Stafman1, Evan F Garner1

  • 1Department of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, AL.

Translational Oncology
|August 29, 2016
PubMed

Insights

Focal adhesion kinase (FAK) inhibition significantly reduced rhabdomyosarcoma (RMS) growth, invasion, and migration while increasing apoptosis. This study highlights FAK as a potential therapeutic target for challenging pediatric RMS tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Rhabdomyosarcoma (RMS) remains a significant therapeutic challenge in pediatric oncology, particularly for metastatic or relapsed cases.
  • Focal adhesion kinase (FAK), a nonreceptor tyrosine kinase, plays a crucial role in various aspects of tumorigenesis, including sarcoma development.

Purpose of the Study:

  • To investigate the presence and role of FAK in pediatric RMS.
  • To evaluate the therapeutic potential of FAK inhibition in RMS.

Main Methods:

  • Analysis of FAK expression and phosphorylation in RMS tumor specimens and cell lines.
  • Inhibition of FAK using RNA interference (RNAi) and small molecule inhibitors in RMS cell lines.
  • Assessment of cellular survival, invasion, migration, and apoptosis following FAK inhibition.
  • Evaluation of FAK inhibition on RMS tumor growth in a xenograft mouse model.

Main Results:

  • FAK was found to be present and phosphorylated in pediatric RMS tumor samples and cell lines.
  • FAK inhibition led to reduced cellular survival, invasion, and migration.
  • FAK inhibition significantly increased apoptosis in RMS cells.
  • Small molecule inhibition of FAK suppressed tumor growth in an RMS xenograft model.

Conclusions:

  • FAK is present and active in RMS, contributing to tumor progression.
  • Targeting FAK demonstrates therapeutic promise for treating pediatric RMS.
  • FAK inhibition offers a potential novel strategy for difficult-to-treat RMS.

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