Sgsm1, or small G protein signaling modulator 1, is a member of a novel protein family. It contains RUN and TBC motifs and is associated with the small G protein (RAP and RAB)-mediated signaling pathway, playing a role in neuronal signal transduction and vesicular transportation pathways. Northern blot analysis shows it is mainly expressed in brain, heart, and testis in humans, and in mouse central nervous system neurons [3].

In gliomas, Sgsm1 is significantly down-regulated, and its low expression is associated with a poor outcome in lower-grade gliomas (LGGs). Functional enrichment analyses suggest it is correlated with immune response, and most immune cells and immune checkpoints are negatively correlated with its expression. Cox regression shows Sgsm1 is an independent prognostic factor in LGG patients (HR = 0.494, 95%CI = 0.311-0.784, P = 0.003), indicating it could be a new prognostic biomarker and potential therapeutic target for LGG treatment [1]. In nasopharyngeal carcinoma, SHISA3 suppresses cell invasion and metastasis by impeding TRIM21-mediated ubiquitination and degradation of Sgsm1 and inhibiting the MAPK pathway activation. Silencing Sgsm1 abolishes the inhibitory effect of SHISA3 on cell migration and invasion, highlighting the SHISA3-TRIM21-Sgsm1 axis as a novel therapeutic target [2].

In summary, Sgsm1 is involved in important signaling pathways, especially those related to neuronal function. Studies, such as in gliomas and nasopharyngeal carcinoma, reveal its potential as a biomarker and therapeutic target in certain cancers. The role of Sgsm1 in these disease conditions provides insights into disease mechanisms and potential treatment strategies.

References:

1. Li, Junsheng, Wang, Jia, Ding, Yaowei, Zhao, Jizong, Wang, Wen. 2022. Prognostic biomarker SGSM1 and its correlation with immune infiltration in gliomas. In BMC cancer, 22, 466. doi:10.1186/s12885-022-09548-7. https://pubmed.ncbi.nlm.nih.gov/35484511/

2. Zhang, Jian, Li, Ying-Qin, Guo, Rui, Ma, Jun, Liu, Na. 2018. Hypermethylation of SHISA3 Promotes Nasopharyngeal Carcinoma Metastasis by Reducing SGSM1 Stability. In Cancer research, 79, 747-759. doi:10.1158/0008-5472.CAN-18-1754. https://pubmed.ncbi.nlm.nih.gov/30573520/

3. Yang, Hao, Sasaki, Takashi, Minoshima, Shinsei, Shimizu, Nobuyoshi. 2007. Identification of three novel proteins (SGSM1, 2, 3) which modulate small G protein (RAP and RAB)-mediated signaling pathway. In Genomics, 90, 249-60. doi:. https://pubmed.ncbi.nlm.nih.gov/17509819/