1. LASP-1 interacts with ErbB2 in ovarian cancer cells.
- Author
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Sidhanth C, Bindhya S, Shabna A, Krishnapriya S, Manasa P, Nagare RP, Joshua T, Sneha S, Murhekar K, and Ganesan TS
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adult, Breast Neoplasms pathology, Carcinoma, Ductal, Breast pathology, Carcinoma, Ovarian Epithelial pathology, Cell Line, Tumor, Cohort Studies, Cytoskeletal Proteins genetics, Female, HEK293 Cells, Humans, LIM Domain Proteins genetics, Lapatinib pharmacology, Middle Aged, Ovarian Neoplasms pathology, Phosphorylation drug effects, Phosphorylation genetics, Plasmids, Protein Kinase Inhibitors pharmacology, Quinazolines pharmacology, Receptor, ErbB-2 genetics, Signal Transduction drug effects, Transfection, Adaptor Proteins, Signal Transducing metabolism, Breast Neoplasms metabolism, Carcinoma, Ductal, Breast metabolism, Carcinoma, Ovarian Epithelial metabolism, Cytoskeletal Proteins metabolism, LIM Domain Proteins metabolism, Ovarian Neoplasms metabolism, Receptor, ErbB-2 metabolism, Signal Transduction genetics
- Abstract
LASP-1 was identified as a protein following mass spectrometric analysis of phosphoproteins consequent to signaling by ErbB2 in SKOV-3 cells. It has been previously identified as an oncogene and is located on chromosomal arm 17q 0.76 Mb centromeric to ErbB2. It is expressed in serous ovarian cancer cell lines as a 40 kDa protein. In SKOV-3 cells, it was phosphorylated and was inhibited by Lapatinib and CP7274714. LASP-1 co-immunoprecipitated with ErbB2 in SKOV-3 cells, suggesting a direct interaction. This interaction and phosphorylation were independent of the kinase activity of ErbB2. Moreover, the binding of LASP-1 to ErbB2 was independent of the tyrosine phosphorylation of LASP-1. LASP-1 was neither expressed on the surface epithelium of the normal ovary nor in the fallopian tube. It was expressed in 28% of ovarian tumours (n = 101) that did not significantly correlate with other clinical factors. In tumours from patients with invasive ductal carcinoma of the breast who had ErbB2 amplification (3+), LASP-1 was expressed in 3/20 (P < 0.001). Analysis of the expression of an independent dataset of ovarian and breast tumours from TCGA showed the significant co-occurrence of ErbB2 and LASP-1 (P < 0.01). These results suggest that LASP-1 and ErbB2 interaction could be important in the pathogenesis of ovarian cancer., (© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
- Published
- 2022
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