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. SIGNIFICANCE: These findings highlight the mechanism by which a newly identified tumor suppressor SHISA3 suppresses invasion and metastasis of nasopharyngeal carcinoma.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Zhang J,Li YQ,Guo R,Wang YQ,Zhang PP,Tang XR,Wen X,Hong XH,Lei Y,He QM,Yang XJ,Sun Y,Ma J,Liu Ndoi
10.1158/0008-5472.CAN-18-1754subject
Has Abstractpub_date
2019-02-15 00:00:00pages
747-759issue
4eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-18-1754journal_volume
79pub_type
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