Scin, also known as scinderin, is a calcium-dependent actin severing and capping protein. It is involved in regulating the F-actin cytoskeleton network, which is crucial for maintaining cell structure and polarity. Additionally, it participates in multiple signaling pathways such as STAT3, NF-κB, and is associated with various biological processes like cell proliferation, migration, and invasion, making it important in normal biological functions and disease development [2,4]. Genetic models, especially knockout models, are valuable for studying its functions.

In a Pik3c3-specific deletion in Sertoli cells (cKO) mouse model, the accumulation of SCIN in cKO Sertoli cells led to the disorder and disassembly of the F-actin cytoskeleton due to the failure of SCIN degradation through the autophagy-lysosome pathway. This disrupted Sertoli cell polarity and impaired spermiogenesis, elucidating a new mechanism for PIK3C3 in maintaining Sertoli cell polarity [1]. In lentivirus-mediated RNA interference studies on human lung carcinoma, prostate carcinoma cells, silencing of SCIN significantly inhibited cell proliferation, induced G0/G1 phase cell cycle arrest, suggesting its role in cancer cell growth [2,4]. In triple-negative breast cancer, RSRC2 transcriptionally inhibits SCIN expression, and SCIN re-expression or knockdown can reverse the cellular function changes caused by RSRC2, indicating its role in breast cancer development [3].

In conclusion, Scin plays essential roles in regulating the actin cytoskeleton and is involved in cell-related processes such as proliferation and polarity maintenance. Studies using KO/CKO mouse models and other loss-of-function experiments have revealed its significance in diseases like infertility due to Sertoli cell dysfunction, and various cancers including lung, prostate, and triple-negative breast cancer. Understanding Scin functions provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Wang, Kehan, Kong, Feifei, Qiu, Yuexin, Hu, Zhibin, Li, Jing. 2023. Autophagy regulation and protein kinase activity of PIK3C3 controls sertoli cell polarity through its negative regulation on SCIN (scinderin). In Autophagy, 19, 2934-2957. doi:10.1080/15548627.2023.2235195. https://pubmed.ncbi.nlm.nih.gov/37450577/

2. Liu, Hongxu, Shi, Daiwang, Liu, Tieqin, Yu, Zhanwu, Zhou, Chuanjiang. 2014. Lentivirus-mediated silencing of SCIN inhibits proliferation of human lung carcinoma cells. In Gene, 554, 32-9. doi:10.1016/j.gene.2014.10.013. https://pubmed.ncbi.nlm.nih.gov/25303873/

3. Zhao, Nan, Ni, Chunsheng, Fan, Shuai, Zhao, Xiulan, Liu, Tieju. 2023. RSRC2 Expression Inhibits Malignant Progression of Triple-Negative Breast Cancer by Transcriptionally Regulating SCIN Expression. In Cancers, 16, . doi:10.3390/cancers16010015. https://pubmed.ncbi.nlm.nih.gov/38201443/

4. Wang, Dong, Sun, Shu-Qing, Yu, Ying-Hao, Yang, Shun-Liang, Tan, Jian-Ming. 2013. Suppression of SCIN inhibits human prostate cancer cell proliferation and induces G0/G1 phase arrest. In International journal of oncology, 44, 161-6. doi:10.3892/ijo.2013.2170. https://pubmed.ncbi.nlm.nih.gov/24212916/