Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • Du, Ruijuan1, 2
  • Huang, Chuntian1, 2
  • Chen, Hanyong3
  • Liu, Kangdong1, 2, 4, 5
  • Xiang, Pu6
  • Yao, Ning2
  • Yang, Lu2
  • Zhou, Liting1, 2
  • Wu, Qiong1, 2
  • Zheng, Yaqiu2
  • Xin, Mingxia2
  • Dong, Zigang7, 8, 9, 10
  • Li, Xiang11, 12, 13, 14
  • 1 Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. , (China)
  • 2 China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China. , (China)
  • 3 The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.
  • 4 The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China. , (China)
  • 5 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, China. , (China)
  • 6 Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, Henan, China. , (China)
  • 7 Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. [email protected] , (China)
  • 8 China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China. [email protected] , (China)
  • 9 The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China. [email protected] , (China)
  • 10 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, China. [email protected] , (China)
  • 11 Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China. [email protected] , (China)
  • 12 China-US (Henan) Hormel Cancer Institute, No. 127, Dongming Road, Jinshui District, Zhengzhou, 450008, Henan, China. [email protected] , (China)
  • 13 The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China. [email protected] , (China)
  • 14 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, China. [email protected] , (China)
Type
Published Article
Journal
Oncogene
Publisher
Nature Publishing Group UK
Publication Date
Jun 22, 2020
Identifiers
DOI: 10.1038/s41388-020-1369-2
PMID: 32572158
Source
Medline
Language
English
License
Unknown

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.

Report this publication

Statistics

Seen <100 times