Mfap5, short for Microfibril Associated Protein 5, is a component of elastic microfibers, playing an important role in the integration of elastic microfibers and regulation of endothelial cell behaviors [3]. It has been implicated in various biological processes and disease conditions, with potential involvement in signaling pathways such as MIF/CD74, IL34/CSF1R, TGF-β/Notch, and PI3K-AKT [1,3,4]. Genetic models, like KO/CKO mouse models, could potentially further clarify its functions.

In cancer research, Mfap5 has been shown to have diverse roles. In colorectal cancer, MFAP5+ fibroblasts interact with tumor-infiltrating myeloid cells, shaping the malignant microenvironment through pro-tumorigenic signaling pathways [1]. In pancreatic cancer, targeting MFAP5 in cancer-associated fibroblasts (CAFs) can sensitize the cancer to PD-L1-based immunochemotherapy by remodeling the matrix [2]. In basal-like breast cancer, MFAP5 promotes cancer progression by activating the EMT program via the TGF-β/Notch pathway [3]. In bladder cancer, CAFs-derived MFAP5 promotes cancer cell proliferation and invasion through the NOTCH2/HEY1 signaling pathway [4]. In contrast, in endometrial cancer, overexpression of MFAP5 inhibits the malignant behaviors of cancer cells, possibly by blocking the AKT/mTOR pathway [5].

In conclusion, Mfap5 is involved in multiple biological processes, especially in cancer-related mechanisms. Its role varies in different types of cancers, either promoting or inhibiting cancer progression. The study of Mfap5 in KO/CKO mouse models, if available, could potentially offer more insights into its functions in these disease conditions, providing potential targets for cancer therapy [1-6].

References:

1. Peng, Zhiwei, Ren, Zihao, Tong, Zhiwei, Zhu, Yansong, Hu, Kongwang. 2023. Interactions between MFAP5 + fibroblasts and tumor-infiltrating myeloid cells shape the malignant microenvironment of colorectal cancer. In Journal of translational medicine, 21, 405. doi:10.1186/s12967-023-04281-6. https://pubmed.ncbi.nlm.nih.gov/37344903/

2. Duan, Yi, Zhang, Xiaozhen, Ying, Honggang, Liang, Tingbo, Bai, Xueli. 2023. Targeting MFAP5 in cancer-associated fibroblasts sensitizes pancreatic cancer to PD-L1-based immunochemotherapy via remodeling the matrix. In Oncogene, 42, 2061-2073. doi:10.1038/s41388-023-02711-9. https://pubmed.ncbi.nlm.nih.gov/37156839/

3. Wu, Yanmei, Wu, Ping, Zhang, Quan, Liu, Xishui, Zheng, Weiqiang. 2019. MFAP5 promotes basal-like breast cancer progression by activating the EMT program. In Cell & bioscience, 9, 24. doi:10.1186/s13578-019-0284-0. https://pubmed.ncbi.nlm.nih.gov/30899449/

4. Zhou, Zheng, Cui, Di, Sun, Meng-Hao, Sun, Feng, Shi, Fei. 2020. CAFs-derived MFAP5 promotes bladder cancer malignant behavior through NOTCH2/HEY1 signaling. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34, 7970-7988. doi:10.1096/fj.201902659R. https://pubmed.ncbi.nlm.nih.gov/32293074/

5. Liang, Guanying, Qi, Zijuan, Du, Chun. 2024. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro. In Open life sciences, 19, 20220990. doi:10.1515/biol-2022-0990. https://pubmed.ncbi.nlm.nih.gov/39759103/