Lgals2, encoding galectin 2, is a member of the galactoside-binding galectin family. It is predominantly expressed in the gastrointestinal tract and is involved in maintaining the strength of the mucus layer and epithelial integrity. It also participates in tissue inflammation, immune response, and cell apoptosis [3].

In triple-negative breast cancer (TNBC), in vivo CRISPR screens identified Lgals2 as a candidate regulator in immune escape. Tumor cell-intrinsic Lgals2 induced an increase in tumor-associated macrophages, as well as M2-like polarization and proliferation of macrophages through the CSF1/CSF1R axis, creating an immunosuppressive microenvironment. Blocking LGALS2 with an inhibitory antibody arrested tumor growth and reversed immune suppression [1]. In colon cancer, genome-wide CRISPR knockout screening identified Lgals2 as an oxidative stress-responsive gene. Gal2-KO mice developed significantly larger tumors than WT mice, and Gal2 overexpression decreased the proliferation of human colon tumor epithelial cells, suggesting Lgals2 has an inhibitory function on colon tumor growth [2].

In conclusion, Lgals2 plays crucial roles in immune regulation and tumor growth. Gene knockout mouse models, such as those in TNBC and colon cancer, have revealed its functions in creating an immunosuppressive tumor microenvironment and inhibiting tumor growth, providing potential therapeutic targets for these diseases.

References:

1. Ji, Peng, Gong, Yue, Jin, Ming-Liang, Hu, Xin, Shao, Zhi-Ming. 2022. In vivo multidimensional CRISPR screens identify Lgals2 as an immunotherapy target in triple-negative breast cancer. In Science advances, 8, eabl8247. doi:10.1126/sciadv.abl8247. https://pubmed.ncbi.nlm.nih.gov/35767614/

2. Li, Haiwen, Zhao, Lixia, Lau, Yeh Siang, Zhang, Chen, Han, Renzhi. 2020. Genome-wide CRISPR screen identifies LGALS2 as an oxidative stress-responsive gene with an inhibitory function on colon tumor growth. In Oncogene, 40, 177-188. doi:10.1038/s41388-020-01523-5. https://pubmed.ncbi.nlm.nih.gov/33110234/

3. Negedu, Muhammed N, Duckworth, Carrie A, Yu, Lu-Gang. 2022. Galectin-2 in Health and Diseases. In International journal of molecular sciences, 24, . doi:10.3390/ijms24010341. https://pubmed.ncbi.nlm.nih.gov/36613785/