Cemip, also known as KIAA1199 and hyaluronan-binding protein involved in hyaluronan depolymerization, is a new member of the hyaluronidase family. It degrades hyaluronic acid (HA), remodels the extracellular matrix, and is involved in regulating various signaling pathways such as WNT and EGFR [2,4,5]. Cemip plays a significant role in many biological processes and diseases, including tumorigenesis, bacterial infection, arthritis, and fibrosis [2].

In cancer, overexpression of Cemip is associated with poor overall survival (OS), disease-free survival (DFS), advanced clinical stage, lymph node metastasis, and poor histological grade [1]. Cemip promotes the proliferation, invasion, and adhesion of various tumor cells, and its depletion in tumour cells impairs brain metastasis [2,3]. In small-cell lung cancer (SCLC), Cemip-mediated HA degradation activates the TLR2/c-Src/ERK1/2 axis, facilitating metastasis [6]. In cardiac remodeling post-myocardial infarction, knockdown of Cemip attenuates fibrosis and improves cardiac function by activating the TSP4 pathway [7].

In conclusion, Cemip is crucial for extracellular matrix remodeling and regulation of signaling pathways. Its functions in cancer metastasis and cardiac remodeling are well-demonstrated through gene knockdown studies. Understanding Cemip's role provides potential therapeutic targets for treating cancer and cardiac fibrosis.

References:

1. Chen, Huan, Wang, Qingting, Liu, Jin, Qiu, Yuanjie, Li, Manxiang. 2023. CEMIP as a prognostic biomarker for cancers: a meta- and bioinformatic analysis. In Expert review of molecular diagnostics, 22, 1107-1115. doi:10.1080/14737159.2022.2168191. https://pubmed.ncbi.nlm.nih.gov/36631437/

2. Liu, Yang, Hu, Gang, Li, Yuetong, Bi, Changlong, Zhai, Aixia. 2023. Research on the biological mechanism and potential application of CEMIP. In Frontiers in immunology, 14, 1222425. doi:10.3389/fimmu.2023.1222425. https://pubmed.ncbi.nlm.nih.gov/37662915/

3. Rodrigues, Gonçalo, Hoshino, Ayuko, Kenific, Candia M, Pisapia, David, Lyden, David. 2019. Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis. In Nature cell biology, 21, 1403-1412. doi:10.1038/s41556-019-0404-4. https://pubmed.ncbi.nlm.nih.gov/31685984/

4. Guo, Song, Guo, Yunfei, Chen, Yuanyuan, Zhang, Chunmei, Chen, Dahu. 2024. The role of CEMIP in cancers and its transcriptional and post-transcriptional regulation. In PeerJ, 12, e16930. doi:10.7717/peerj.16930. https://pubmed.ncbi.nlm.nih.gov/38390387/

5. Chen, Yu, Zhou, Hu, Jiang, Wen-Jing, Jiang, Yan, Xia, Bai-Rong. 2021. The role of CEMIP in tumors: An update based on cellular and molecular insights. In Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 146, 112504. doi:10.1016/j.biopha.2021.112504. https://pubmed.ncbi.nlm.nih.gov/34922110/

6. Li, Li, Shen, Xiaoju, Mo, Xiaoxiang, Mao, Naiquan, Yang, Jie. 2023. CEMIP-mediated hyaluronan metabolism facilitates SCLC metastasis by activating TLR2/c-Src/ERK1/2 axis. In Biochimica et biophysica acta. Molecular cell research, 1870, 119451. doi:10.1016/j.bbamcr.2023.119451. https://pubmed.ncbi.nlm.nih.gov/36931608/

7. Zha, Yafang, Luo, Xueyang, Ge, Zhuowang, Li, Yanyan, Zhang, Song. 2024. KIAA1199/CEMIP knockdown attenuates cardiac remodeling post myocardial infarction by activating TSP4 pathway in mice. In Biochimica et biophysica acta. Molecular basis of disease, 1870, 167473. doi:10.1016/j.bbadis.2024.167473. https://pubmed.ncbi.nlm.nih.gov/39173890/