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.
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In this issue Oldham and colleagues (pp. 57–74) have performed extensive structural and kinetic characterization of the SAT enzyme from the antibiotic-resistant pathogen Neisseria gonorrhoeae. Using X-ray crystallography, we have solved the structures of NgSAT with the non-natural ligand, l-malate. They present data which could be explored to combat the rise of antimicrobial resistant N. gonorrhoeae. The cover image shows a ribbon diagram of the NgSAT trimer illustrating the position and formation of the active site between two adjacent monomers. The image is courtesy of Joanna Hicks.
LASP-1 interacts with ErbB2 in ovarian cancer cells
Chirukandath Sidhanth, Sadhanandhan Bindhya, Aboo Shabna, Shyama Krishnapriya, Pacharla Manasa, Rohit Pravin Nagare, Thanda Joshua, Smarkan Sneha, Kanchan Murhekar, Trivadi Sundaram Ganesan; LASP-1 interacts with ErbB2 in ovarian cancer cells. Biochem J 14 January 2022; 479 (1): 23–38. doi: https://doi.org/10.1042/BCJ20210173
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