Somatic mutational analysis of FAK in breast cancer: A novel gain-of-function mutation due to deletion of exon 33
| Autor: | Xiangfan Liu, Changqiang Chen, Zhidong Gu, Ling Yao, Qishi Fan, Peihua Ni, Xin-Min Zheng, Xu-Qian Fang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Somatic cell
DNA Mutational Analysis Mutant Biophysics Breast Neoplasms Biology medicine.disease_cause Biochemistry Focal adhesion Exon Breast cancer Tumor Cells Cultured medicine Humans Cell adhesion Molecular Biology Mutation Exons Cell Biology medicine.disease Molecular biology Focal Adhesion Protein-Tyrosine Kinases Female biological phenomena cell phenomena and immunity Gene Deletion Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Biochemical and Biophysical Research Communications. 443:363-369 |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect