title: Somatic mutational analysis of FAK in breast cancer: a novel gain-of-function mutation due to deletion of exon 33.
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.affiliation: Department of Clinical Laboratory, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, PR China.
authors.forename: Xu-Qian
authors.initials: XQ
authors.lastname: Fang
authors.affiliation: Faculty of Medical Laboratory Science, Shanghai JiaoTong University School of Medicine, Shanghai, PR China.
authors.forename: Xiang-Fan
authors.initials: XF
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai JiaoTong University School of Medicine, Shanghai, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Clinical Laboratory, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, PR China.
authors.forename: Chang-Qiang
authors.initials: CQ
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, PR China.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Gu
authors.affiliation: Faculty of Medical Laboratory Science, Shanghai JiaoTong University School of Medicine, Shanghai, PR China.
authors.forename: Pei-Hua
authors.initials: PH
authors.lastname: Ni
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanghai JiaoTong University School of Medicine, Shanghai, PR China; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Zheng
authors.affiliation: Department of Clinical Laboratory, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, PR China. Electronic address: qishifan@126.com.
authors.forename: Qi-Shi
authors.initials: QS
authors.lastname: Fan
mesh_terms: D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D009154:Mutation / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: Breast cancer; Focal adhesion kinase (FAK); Migration; Signal pathway; Splicing mutant; c-Src