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

Highlights: •A novel FAK splicing mutation identified in breast tumor. •FAK-Del33 mutation promotes cell migration and invasion. •FAK-Del33 mutation regulates FAK/Src signal pathway. -- Abstract: 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.
Authors:
 [1] ;  [2] ;  [3] ; ;  [1] ;  [2] ;  [3] ;  [4] ;  [1]
  1. Department of Clinical Laboratory, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai (China)
  2. Faculty of Medical Laboratory Science, Shanghai JiaoTong University School of Medicine, Shanghai (China)
  3. Department of Biochemistry and Molecular Biology, Shanghai JiaoTong University School of Medicine, Shanghai (China)
  4. (United States)
Publication Date:
OSTI Identifier:
22242254
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 443; Journal Issue: 2; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; HEALING; MAMMARY GLANDS; METASTASES; MIGRATION; MUTANTS; MUTATIONS; NEOPLASMS; PHOSPHORYLATION; SPLICING; THYROID; TUMOR CELLS; WOUNDS