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

Journal Article · Fri Jan 10 04:00:00 EST 2014 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2013.11.134· OSTI ID:22242254

Fang, Xu-Qian ^[1]; Liu, Xiang-Fan ^[2]; Yao, Ling ^[3]; Chen, Chang-Qiang; Gu, Zhi-Dong ^[1]; Ni, Pei-Hua ^[2]; Zheng, Xin-Min ^[3]; Fan, Qi-Shi ^[1]

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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)

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.

• OSTI ID: 22242254
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 443; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
HEALING
MAMMARY GLANDS
METASTASES
MIGRATION
MUTANTS
MUTATIONS
NEOPLASMS
PHOSPHORYLATION
SPLICING
THYROID
TUMOR CELLS
WOUNDS