Cotl1, or Coactosin-Like Protein 1, is a cytoskeleton-associated protein belonging to the actin-depolymerizing factor (ADF)/cofilin family [3,4]. It strongly binds to F-actin and is involved in regulating cell migration, adhesion, and signaling [3]. It may also be associated with 5-lipoxygenase, influencing related pathways [5,6]. In general, it plays a crucial role in various biological processes such as neuronal migration and tumor progression [3,4]. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying its functions.

In intracerebral hemorrhage (ICH), machine-learning-based analysis integrating bulk and single-cell RNA data showed that Cotl1 is closely associated with high oxidative stress (OS) activity. After ICH, it might penetrate the brain via monocytes, localize within microglia, and enhance OS activity [1]. In glioblastoma (GBM), Cotl1 has high expression in human GBM tissues, is related to recurrence and prognosis, and promotes GBM cell proliferation in vitro and tumor growth in vivo [2]. Pan-cancer analysis indicates Cotl1 is highly expressed in most cancers, correlates with decreased survival in Glioma, Glioblastoma multiforme, and pan-kidney cohorts, and is associated with DNA and RNA stemness, immunological checkpoints, immune infiltration cells, and other immunotherapy-related factors [3]. In breast cancer, its high expression is correlated with poor prognosis and immune cell infiltration, and it can regulate cell migration and tumor metastasis through the miR-30c-5p/COTL1 pathway [5,7]. In mouse corticogenesis, overexpression of Cotl1 impairs neuronal migration, delays the migration of late-born neurons, and disturbs the morphology of migrating neurons [4]. Further studies with mutant vectors (Cotl1-ABM and Cotl1-K131A) in mouse neocortical development showed that Cotl1 affects neuronal migration and the proliferation and mitotic activity of neural progenitors (NPs) [6].

In conclusion, Cotl1 is significantly involved in multiple biological processes. Studies using mouse models, especially those related to its overexpression or mutation, have revealed its role in diseases such as ICH, glioblastoma, and breast cancer, as well as in neuronal development. These findings contribute to understanding the underlying mechanisms of these diseases and may provide potential therapeutic targets.

References:

1. Du, Chaonan, Wang, Cong, Liu, Zhiwei, Li, Zhenxing, Ma, Chiyuan. 2024. Machine learning algorithms integrate bulk and single-cell RNA data to unveil oxidative stress following intracerebral hemorrhage. In International immunopharmacology, 137, 112449. doi:10.1016/j.intimp.2024.112449. https://pubmed.ncbi.nlm.nih.gov/38865753/

2. Shao, Shike, Fan, Yongjun, Zhong, Chongpei, Zhu, Xianlong, Zhu, Jiaqiu. 2020. Coactosin-Like Protein (COTL1) Promotes Glioblastoma (GBM) Growth in vitro and in vivo. In Cancer management and research, 12, 10909-10917. doi:10.2147/CMAR.S246030. https://pubmed.ncbi.nlm.nih.gov/33154670/

3. Wang, Xiaoyun, Bai, Yuwei, Wang, Bei. 2024. Coactosin-Like Protein 1 (COTL1) Could Be an Immunological and Prognostic Biomarker: From Pan-Cancer Analysis to Low-Grade Glioma Validation. In Journal of inflammation research, 17, 1805-1820. doi:10.2147/JIR.S453509. https://pubmed.ncbi.nlm.nih.gov/38523681/

4. Li, Guohong, Yin, Yupeng, Chen, Jiong, Chen, Shulin, Zhao, Shanting. . Coactosin-like protein 1 inhibits neuronal migration during mouse corticogenesis. In Journal of veterinary science, 19, 21-26. doi:10.4142/jvs.2018.19.1.21. https://pubmed.ncbi.nlm.nih.gov/28385010/

5. Wang, Bei, Zhao, Limiao, Chen, Dandan. 2022. Coactosin-Like Protein in Breast Carcinoma: Friend or Foe? In Journal of inflammation research, 15, 4013-4025. doi:10.2147/JIR.S362606. https://pubmed.ncbi.nlm.nih.gov/35873386/

6. Liu, Mengmeng, Li, Guohong, Wang, Mengli, Zhu, Xiaoyan, Zhao, Shanting. 2018. Further studies about Coactosin-like protein-1 affecting the migration of mouse neocortical neurons. In Journal of molecular histology, 49, 519-530. doi:10.1007/s10735-018-9790-3. https://pubmed.ncbi.nlm.nih.gov/30128637/

7. Pei, Bei, Li, Tongyang, Qian, Qi, Zhu, Yulan, Xu, Lingyun. . Downregulation of microRNA-30c-5p was responsible for cell migration and tumor metastasis via COTL1-mediated microfilament arrangement in breast cancer. In Gland surgery, 9, 747-758. doi:10.21037/gs-20-472. https://pubmed.ncbi.nlm.nih.gov/32775265/