SDCBP/MDA-9/syntenin phosphorylation by AURKA promotes esophageal squamous cell carcinoma progression through the EGFR-PI3K-Akt signaling pathway

Ruijuan Du, Chuntian Huang, Hanyong Chen, Kangdong Liu, Pu Xiang, Ning Yao, Lu Yang, Liting Zhou, Qiong Wu, Yaqiu Zheng, Mingxia Xin, Zigang Dong, Xiang Li

Research output: Contribution to journalArticle

Abstract

SDCBP is an adapter protein containing two tandem PDZ domains mediating cell adhesion. The role and underlying molecular mechanism of SDCBP in ESCC remain obscure. Here, we report that SDCBP is frequently overexpressed in ESCC tissues and cells compared to normal controls and that its overexpression is correlated with late clinical stage and predicts poor prognosis in ESCC patients. Functionally, high expression of SDCBP is positively related to ESCC progression both in vitro and in vivo. Furthermore, mechanistic studies show that SDCBP activates the EGFR-PI3K-Akt signaling pathway by binding to EGFR and preventing EGFR internalization. Moreover, we provide evidence that AURKA binds to SDCBP and phosphorylates it at the Ser131 and Thr200 sites to inhibit ubiquitination-mediated SDCBP degradation. More importantly, the sites at which AURKA phosphorylates SDCBP are crucial for the EGFR signaling-mediated oncogenic function of SDCBP. Taken together, we propose that SDCBP phosphorylation by AURKA prevents SDCBP degradation and promotes ESCC tumor growth through the EGFR-PI3K-Akt signaling pathway. Our findings unveil a new AURKA–SDCBP–EGFR axis that is involved in ESCC progression and provide a promising therapeutic target for ESCC treatment in the clinic.

Original languageEnglish (US)
Pages (from-to)5405-5419
Number of pages15
JournalOncogene
Volume39
Issue number31
DOIs
StatePublished - Jul 30 2020

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    Du, R., Huang, C., Chen, H., Liu, K., Xiang, P., Yao, N., Yang, L., Zhou, L., Wu, Q., Zheng, Y., Xin, M., Dong, Z., & Li, X. (2020). SDCBP/MDA-9/syntenin phosphorylation by AURKA promotes esophageal squamous cell carcinoma progression through the EGFR-PI3K-Akt signaling pathway. Oncogene, 39(31), 5405-5419. https://doi.org/10.1038/s41388-020-1369-2