Lasp1-KO Mouse

Lasp1, also known as LIM and SH3 protein 1, was initially identified as a structural cytoskeletal protein with scaffolding function. It is now known to have additional roles in cell signaling and gene expression, especially in tumor cells. These functions are mainly regulated by site-specific phosphorylation. Lasp1 is involved in chemokine receptor, and PI3K/AKT signaling, and also plays a role in epigenetics, transcriptional regulation, and modulation of oncogenic mRNA translation in the nucleus. Its cytoskeletal function includes not only the known canonical F-actin binding properties but also newly identified roles. Zebrafish is a useful vertebrate model for studying Lasp1 function in developmental biology and organogenesis [1,2].

In a mouse model of rheumatoid arthritis, deletion of Lasp1 reduces arthritic joint destruction. This shows that Lasp1 functions in cellular junction formation and inflammatory tissue remodelling in destructive arthritis, suggesting it could be a potential target for treating inflammatory joint disorders [3]. In lung cancer cells, silencing Lasp1 blunts cell invasion, migration, and proliferation induced by TGF-β1, indicating that Lasp1 is involved in the TGF-β1/Smad/Snail signaling pathway and epithelial-mesenchymal transition (EMT) [4].

In conclusion, Lasp1 is a multi-functional protein involved in cell structure, physiological processes, and cell signaling. Its role in cancer, such as promoting tumor cell proliferation, migration, and invasion, and in embryonic development has been revealed through studies using animal models like zebrafish and mice. Understanding Lasp1 function provides insights into disease mechanisms and potential therapeutic targets for diseases including cancer and inflammatory joint disorders.

References:

1. Butt, Elke, Howard, Cory M, Raman, Dayanidhi. 2022. LASP1 in Cellular Signaling and Gene Expression: More than Just a Cytoskeletal Regulator. In Cells, 11, . doi:10.3390/cells11233817. https://pubmed.ncbi.nlm.nih.gov/36497077/

2. Grossi, Ilaria, Schiavone, Marco, Cannone, Elena, Salvi, Alessandro, De Petro, Giuseppina. 2022. Lasp1 Expression Is Implicated in Embryonic Development of Zebrafish. In Genes, 14, . doi:10.3390/genes14010035. https://pubmed.ncbi.nlm.nih.gov/36672776/

3. Beckmann, Denise, Römer-Hillmann, Anja, Krause, Annika, Pap, Thomas, Korb-Pap, Adelheid. 2021. Lasp1 regulates adherens junction dynamics and fibroblast transformation in destructive arthritis. In Nature communications, 12, 3624. doi:10.1038/s41467-021-23706-8. https://pubmed.ncbi.nlm.nih.gov/34131132/

4. Xue, Qingming, Jiang, Hong, Wang, Jinjie, Wei, Dongshan. 2021. LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway. In Canadian respiratory journal, 2021, 5277409. doi:10.1155/2021/5277409. https://pubmed.ncbi.nlm.nih.gov/34912481/