journal contribution
posted on 2023-03-31, 02:42 authored by Jian Zhang, Ying-Qin Li, Rui Guo, Ya-Qin Wang, Pan-Pan Zhang, Xin-Ran Tang, Xin Wen, Xiao-Hong Hong, Yuan Lei, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Jun Ma, Na Liu Supplementary Tables S1-S5: -Table S1. Primers used in this study. Table S2. Antibodies used in this study. Table S3. Sequencing of anti-SHISA3 immunoprecipitation complex by mass spectrometry. Table S4. Sequencing of anti-SGSM1 immunoprecipitation complex by mass spectrometry. Table S5. The possible ubiquitination sites of SGSM1 C-terminal.
Funding
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province
History
ARTICLE ABSTRACT
Altered DNA methylation is a key feature of cancer, and aberrant methylation is important in nasopharyngeal carcinoma (NPC) development. However, the methylation mechanisms underlying metastasis of NPC remain unclear. Analyzing data from public databases and conducting our own experiments, we report here that promoter hypermethylation of SHISA3 is common and contributes to the downregulation of this gene in many types of tumors, including NPC. SHISA3 suppressed NPC cell invasion and metastasis in vitro and in vivo by impeding the E3 ubiquitin ligase tripartite motif containing 21 (TRIM21)–mediated ubiquitination and degradation small G protein signaling modulator 1 (SGSM1) and by inhibiting the MAPK pathway activation. Silencing SGSM1 abrogated the inhibitory effect of SHISA3 on NPC cell migration and invasion. This newly identified SHISA3–TRIM21–SGSM1 axis could be a novel therapeutic target in NPC.
These findings highlight the mechanism by which a newly identified tumor suppressor SHISA3 suppresses invasion and metastasis of nasopharyngeal carcinoma.
