FLOT2 promotes nasopharyngeal carcinoma progression through suppression of TGF-ß pathway via facilitating CD109 expression
In nasopharyngeal carcinoma (NPC), the TGF-ß/SMAD pathway genes are altered with inactive TGF-ß signal, but the mechanisms remain unclear. Flotillin 2 (FLOT2) is a highly expressed protein in NPC, and is crucial for NPC progression. We show that FLOT2 negatively regulated TGF-ß signaling pathway via up-regulating CD109 expression. FLOT2 increased CD109 transcription by stabilizing STAT3, which is identified as the activating transcription factor of CD109. FLOT2 interacted with STAT3 directly and increased the stability of STAT3 by inhibiting K48-linked polyubiquitination. CD109 could rescue the functional changes of NPC cells resulted from FLOT2 alteration. Expression of FLOT2 and CD109 was positively correlated, and was significantly higher in NPC tissues than in the normal nasopharyngeal epithelial tissues. Patients with high expression of both FLOT2 and CD109 presented poorer overall survival and disease-free survival compared those with high expression of one protein alone. In conclusion, FLOT2 promotes the development of NPC by inhibiting TGF-ß signaling pathway via stimulating the expression of CD109 by stabilizing STAT3, which provides novel potential therapeutic strategy for NPC treatment. Overall design: Expression data and the differentially expressed mRNAs in 5-8F-control and 5-8F-shFLOT2 cells were analysed using RNA-seq