LGALS1, encoding Galectin-1, is a glycan-binding protein that regulates both intracellular processes like signal transduction and extracellular ones such as immunity and leukocyte mobilization, with a well-known role in RAS signaling [2]. It is involved in various biological processes and is of great significance in maintaining cell survival. Genetic models, including gene knockout mouse models, have been crucial in understanding its functions.

In glioblastoma, single-cell profiling and zebrafish avatar models identified LGALS1 as a primary regulator of immunosuppression, as GBM-induced GAM polarization and related features correlated with patient survival and LGALS1 was found to be key in these processes [1]. In acute myeloid leukemia (AML), LGALS1 acts as a pro-survival molecule. Reduction of its expression in an in vivo murine OCI-AML3 xenograft model led to significantly longer survival of mice, and elevated LGALS1 mRNA in AML patients was associated with shorter disease-free survival [2]. In intrahepatic cholangiocarcinoma (ICC), LGALS1+ fibroblasts promoted tumor cell proliferation and migration, and silencing LGALS1 in cancer-associated fibroblasts suppressed tumor-related activities in vitro and in vivo [3]. In relapsed/refractory AML, chemotherapy-induced cellular reprogramming led to upregulation of LGALS1 in quiescent stem-like cells associated with chemoresistance, and LGALS1 inhibitor could enhance chemotherapy [4].

In conclusion, LGALS1 is essential in regulating cell survival, immune modulation, and tumor-related processes. Gene knockout and other genetic models have been instrumental in revealing its role in diseases such as glioblastoma, AML, and ICC, providing potential therapeutic targets for these diseases.

References:

1. Finotto, Lise, Cole, Basiel, Giese, Wolfgang, De Smet, Frederik, Gerhardt, Holger. 2023. Single-cell profiling and zebrafish avatars reveal LGALS1 as immunomodulating target in glioblastoma. In EMBO molecular medicine, 15, e18144. doi:10.15252/emmm.202318144. https://pubmed.ncbi.nlm.nih.gov/37791581/

2. Ruvolo, Peter P, Ma, Huaxian, Ruvolo, Vivian R, Post, Sean M, Andreeff, Michael. 2020. LGALS1 acts as a pro-survival molecule in AML. In Biochimica et biophysica acta. Molecular cell research, 1867, 118785. doi:10.1016/j.bbamcr.2020.118785. https://pubmed.ncbi.nlm.nih.gov/32590026/

3. Cao, Qiqi, Yang, Jinxian, Jiang, Lixuan, Wang, Hongyang, Wen, Wen. . Single-cell analysis defines LGALS1+ fibroblasts that promote proliferation and migration of intrahepatic cholangiocarcinoma. In Journal of molecular cell biology, 16, . doi:10.1093/jmcb/mjae023. https://pubmed.ncbi.nlm.nih.gov/38862197/

4. Li, Kening, Du, Yuxin, Cai, Yun, Hong, Ming, Qian, Sixuan. 2022. Single-cell analysis reveals the chemotherapy-induced cellular reprogramming and novel therapeutic targets in relapsed/refractory acute myeloid leukemia. In Leukemia, 37, 308-325. doi:10.1038/s41375-022-01789-6. https://pubmed.ncbi.nlm.nih.gov/36543880/