Farp1-KO Mouse

FARP1, or FERM, Rho/ArhGEF, and Pleckstrin domain protein 1, is a multi-domain protein involved in multiple biological processes. It functions as a guanine nucleotide exchange factor (GEF) for RhoGTPases like RAC1 and RhoA, and is associated with pathways such as the Wnt/PCP pathway [5]. It plays a crucial role in neuronal development, cell motility, and synapse formation, and is thus of great biological importance. Genetic models, such as gene knockout models, can help further explore its functions.

In non-small-cell lung cancer, an sQTL variant rs35861926 promotes FARP1 exon 20 skipping, down-regulating the expression of the long transcript FARP1-011 which promotes the migration and proliferation of lung adenocarcinoma cells [1]. In cutaneous melanoma, knockdown of FARP1 in A-375 cells inhibits cell proliferation, migration, and invasion, and it modulates the MAPK signaling pathway [2]. In human lung adenocarcinoma, FARP1 is identified as an essential Rac-GEF responsible for Rac1-mediated cell migration upon EGFR and c-Met activation [3]. In advanced gastric cancer, high FARP1 expression is associated with poor prognosis, and knockdown in gastric cancer cells decreases cell motility [4].

In conclusion, FARP1 is significantly involved in cell proliferation, migration, and invasion processes across multiple cancer types, as revealed through various functional studies. These findings from model-based research, especially those related to loss-of-function experiments, contribute to understanding the role of FARP1 in cancer development, providing potential therapeutic targets for these diseases.

References:

1. Wang, Yuzhuo, Ding, Yue, Liu, Su, Shen, Hongbing, Ma, Hongxia. 2023. Integrative splicing-quantitative-trait-locus analysis reveals risk loci for non-small-cell lung cancer. In American journal of human genetics, 110, 1574-1589. doi:10.1016/j.ajhg.2023.07.008. https://pubmed.ncbi.nlm.nih.gov/37562399/

2. Chen, Zhao-Hui, Wang, Li-Hua. . FARP1 Facilitates Cell Proliferation Through Modulating MAPK Signaling Pathway in Cutaneous Melanoma. In The American Journal of dermatopathology, 41, 908-913. doi:10.1097/DAD.0000000000001426. https://pubmed.ncbi.nlm.nih.gov/31021836/

3. Cooke, Mariana, Kreider-Letterman, Gabriel, Baker, Martin J, García-Mata, Rafael, Kazanietz, Marcelo G. . FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma. In Cell reports, 37, 109905. doi:10.1016/j.celrep.2021.109905. https://pubmed.ncbi.nlm.nih.gov/34731623/

4. Hirano, Takuro, Shinsato, Yoshinari, Tanabe, Kan, Furukawa, Tatsuhiko, Natsugoe, Shoji. 2020. FARP1 boosts CDC42 activity from integrin αvβ5 signaling and correlates with poor prognosis of advanced gastric cancer. In Oncogenesis, 9, 13. doi:10.1038/s41389-020-0190-7. https://pubmed.ncbi.nlm.nih.gov/32029704/

5. Domínguez-Berzosa, Laura, Cantarero, Lara, Rodríguez-Sanz, María, Palau, Francesc, Hoenicka, Janet. 2024. ANKK1 Is a Wnt/PCP Scaffold Protein for Neural F-ACTIN Assembly. In International journal of molecular sciences, 25, . doi:10.3390/ijms251910705. https://pubmed.ncbi.nlm.nih.gov/39409035/