Mmp21, encoding matrix metallopeptidase 21, is a gene with important functions in embryogenesis and tumor progression. It is involved in extracellular matrix remodeling, which is crucial for normal left-right asymmetry establishment during embryonic development. In tumor-related processes, it may be associated with invasion and metastasis through certain signaling pathways [1,4].

In human studies, recessive mutations in MMP21 have been identified in patients with heterotaxy, a condition resulting from abnormal left-right asymmetry in embryonic development. Mmp21-mutant mice showed heterotaxy and abnormal cardiac looping, suggesting its essential role in laterality establishment in vertebrates [3,6]. In zebrafish, knockdown of mmp21 led to heart looping disorders, further validating its function in left-right patterning [2]. In cancer research, in hepatocellular carcinoma, ADAM17 promotes invasion via upregulation of MMP21, indicating its role in tumor invasion [4]. Also, overexpression of MMP21 in gastric cancer is associated with cancer progression and poor prognosis [5].

In conclusion, Mmp21 is vital for normal left-right asymmetry during embryonic development as demonstrated by gene-modified animal models. In the context of diseases, its role in cancer invasion and metastasis, as well as in congenital disorders like heterotaxy, makes it an important target for further research, potentially providing insights into disease mechanisms and new therapeutic strategies.

References:

1. Nakai, Kazuki, Lin, Hancheng, Yamano, Shotaro, Fujita, Yasuyuki, Kon, Shunsuke. 2023. Wnt activation disturbs cell competition and causes diffuse invasion of transformed cells through NF-κB-MMP21 pathway. In Nature communications, 14, 7048. doi:10.1038/s41467-023-42774-6. https://pubmed.ncbi.nlm.nih.gov/37923722/

2. Qin, Xi-Ji, Xu, Meng-Meng, Ye, Jia-Jun, Sun, Kun, Xu, Yue-Juan. 2022. De novo disruptive heterozygous MMP21 variants are potential predisposing genetic risk factors in Chinese Han heterotaxy children. In Human genomics, 16, 41. doi:10.1186/s40246-022-00409-9. https://pubmed.ncbi.nlm.nih.gov/36123719/

3. Guimier, Anne, Gabriel, George C, Bajolle, Fanny, Lo, Cecilia W, Gordon, Christopher T. 2015. MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates. In Nature genetics, 47, 1260-3. doi:10.1038/ng.3376. https://pubmed.ncbi.nlm.nih.gov/26437028/

4. Xiang, Yuqi, Liu, Liyu, Wang, Ying, Peng, Jinwu, Feng, Deyun. 2020. ADAM17 promotes the invasion of hepatocellular carcinoma via upregulation MMP21. In Cancer cell international, 20, 516. doi:10.1186/s12935-020-01556-6. https://pubmed.ncbi.nlm.nih.gov/33100908/

5. Zhang, Jizhen, Pan, Qi, Yan, Wenhui, He, Xujun, Zhao, Zhongsheng. 2018. Overexpression of MMP21 and MMP28 is associated with gastric cancer progression and poor prognosis. In Oncology letters, 15, 7776-7782. doi:10.3892/ol.2018.8328. https://pubmed.ncbi.nlm.nih.gov/29731903/

6. Perles, Zeev, Moon, Sungjin, Ta-Shma, Asaf, Elpeleg, Orly, Katsanis, Nicholas. 2015. A human laterality disorder caused by a homozygous deleterious mutation in MMP21. In Journal of medical genetics, 52, 840-7. doi:10.1136/jmedgenet-2015-103336. https://pubmed.ncbi.nlm.nih.gov/26429889/