LASP-1 interacts with ErbB2 in ovarian cancer cells

• DOI: 10.1042/bcj20210173
• Publication Date: 2021-12-09T10:37:16Z
• Authors: Chirukandath Sidh...; Sadhanandhan Bindhya; Aboo Shabna; Shyama Krishnapriya; Pacharla Manasa; Rohit Pravin Nagare; Thanda Joshua; Smarkan Sneha; Kanchan Murhekar; Trivadi Sundaram ...
• Keywords: Adult; Ovarian Neoplasms; Receptor, ErbB-2; Carcinoma, Ductal, Breast; Breast Neoplasms; Lapatinib; Carcinoma, Ovarian Epithelial; LIM Domain Proteins; Middle Aged; 3. Good health; Cohort Studies; Cytoskeletal Proteins; 03 medical and health sciences; HEK293 Cells; 0302 clinical medicine; Cell Line, Tumor; Quinazolines; Humans; Female; Phosphorylation; Protein Kinase Inhibitors; Adaptor Proteins, Signal Transducing; Plasmids

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.