Somatic mutational analysis of FAK in breast cancer: a novel gain-of-function mutation due to deletion of exon 33

Biochem Biophys Res Commun. 2014 Jan 10;443(2):363-9. doi: 10.1016/j.bbrc.2013.11.134. Epub 2013 Dec 19.


Focal adhesion kinase (FAK) regulates cell adhesion, migration, proliferation, and survival. We identified a novel splicing mutant, FAK-Del33 (exon 33 deletion, KF437463), in both breast and thyroid cancers through colony sequencing. Considering the low proportion of mutant transcripts in samples, this mutation was detected by TaqMan-MGB probes based qPCR. In total, three in 21 paired breast tissues were identified with the FAK-Del33 mutation, and no mutations were found in the corresponding normal tissues. When introduced into a breast cell line through lentivirus infection, FAK-Del33 regulated cell motility and migration based on a wound healing assay. We demonstrated that the expression of Tyr397 (main auto-phosphorylation of FAK) was strongly increased in FAK-Del33 overexpressed breast tumor cells compared to wild-type following FAK/Src RTK signaling activation. These results suggest a novel and unique role of the FAK-Del33 mutation in FAK/Src signaling in breast cancer with significant implications for metastatic potential.

Keywords: Breast cancer; Focal adhesion kinase (FAK); Migration; Signal pathway; Splicing mutant; c-Src.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics*
  • DNA Mutational Analysis*
  • Exons / genetics*
  • Female
  • Focal Adhesion Protein-Tyrosine Kinases / genetics*
  • Gene Deletion
  • Humans
  • Mutation / genetics*
  • Tumor Cells, Cultured


  • Focal Adhesion Protein-Tyrosine Kinases