SRPX2, also known as Sushi-repeat-containing protein, X-linked, 2, is a gene located on Xq22.1 encoding a secreted protein highly expressed in neurons of the cerebral cortex. It has been implicated in multiple biological functions.

In the nervous system, it is related to neurodevelopment, learning, and rolandic seizure [2]. In cancer biology, it is associated with pathways like PI3K/AKT, FAK, and Wnt/β-catenin, influencing processes such as cell proliferation, migration, invasion, and chemoresistance [1,3,4,5].

Mouse models have been crucial in studying SRPX2. For instance, in mouse models, silencing SRPX2 and injecting a specific variant (p.Asn327Ser) result in alterations in neuronal migration in the cerebral cortex and epilepsy, demonstrating its role in neurodevelopment [2]. In papillary thyroid cancer, mouse xenograft models showed that SRPX2 silencing suppressed tumor proliferation and migration in vivo, suggesting its pro-tumorigenic role in this cancer type [3].

In pancreatic cancer, high SRPX2 levels are associated with poor prognosis, and si-SRPX2 enhanced chemosensitivity of pancreatic cancer cell lines, indicating its role in chemoresistance [4]. In esophageal squamous cell carcinoma, knockdown of SRPX2 inhibited cell proliferation, metastasis, and promoted chemosensitivity through inactivation of the Wnt/β-catenin signaling pathway [5].

In conclusion, SRPX2 plays diverse and significant roles in both neurodevelopment and cancer-related biological processes. Mouse models, especially those involving SRPX2 knockdown or KO/CKO, have been instrumental in uncovering its functions in these areas, providing potential targets for treating neurological disorders and cancers [2,3,4,5].

References:

1. Guo, Haiwei, Liu, Ruiqi, Wu, Jiajun, Lu, Yanwei, Zhang, Haibo. 2023. SRPX2 promotes cancer cell proliferation and migration of papillary thyroid cancer. In Clinical and experimental medicine, 23, 4825-4834. doi:10.1007/s10238-023-01113-1. https://pubmed.ncbi.nlm.nih.gov/37306872/

2. Schirwani, Schaida, McConnell, Vivienne, Willoughby, Josh, Balasubramanian, Meena. 2018. Exploring the association between SRPX2 variants and neurodevelopment: How causal is it? In Gene, 685, 50-54. doi:10.1016/j.gene.2018.10.067. https://pubmed.ncbi.nlm.nih.gov/30393191/

3. Luo, Ning, Tan, Yanfei, Deng, Hong, Zhu, Hongbo, Liu, Chang. 2022. SRPX2 Promotes Tumor Proliferation and Migration via the FAK Pathway in Papillary Thyroid Carcinoma. In Journal of oncology, 2022, 5821545. doi:10.1155/2022/5821545. https://pubmed.ncbi.nlm.nih.gov/36385962/

4. Gao, Zhenyuan, Wu, Jisong, Wu, Xiao, Zheng, Jialei, Ou, Yimei. 2020. SRPX2 boosts pancreatic cancer chemoresistance by activating PI3K/AKT axis. In Open medicine (Warsaw, Poland), 15, 1072-1082. doi:10.1515/med-2020-0157. https://pubmed.ncbi.nlm.nih.gov/33336063/

5. He, Fei, Wang, Haojie, Li, Yong, Wang, Qianqian, Shi, Gongning. 2018. SRPX2 knockdown inhibits cell proliferation and metastasis and promotes chemosensitivity in esophageal squamous cell carcinoma. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 109, 671-678. doi:10.1016/j.biopha.2018.10.042. https://pubmed.ncbi.nlm.nih.gov/30551519/