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Research Paper|Volume 11, Issue 20|pp 8951—8968

LDLRAD2 overexpression predicts poor prognosis and promotes metastasis by activating Wnt/β-catenin/EMT signaling cascade in gastric cancer

Yucai Wei1,2, Fan Zhang2, Tong Zhang3, Yating Zhang2, Hao Chen1,2, Furong Wang2,4, Yumin Li1,2
  • 1Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou 730000, China
  • 2Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou 730000, China
  • 3Department of Hepatic Surgery, Liver Transplant Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • 4Department of Pathology, Lanzhou University Second Hospital, Lanzhou 730000, China
* Equal contribution
Received: March 23, 2019Accepted: October 5, 2019Published: October 24, 2019
https://doi.org/10.18632/aging.102359

Copyright © 2019 Wei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The therapeutic strategies for advanced gastric cancer (GC) remain unsatisfying and limited. Therefore, it is still imperative to fully elucidate the mechanisms underlying GC aggressive progression. The prognostic value and biological functions of low density lipoprotein receptor class A domain containing protein 2 (LDLRAD2) in GC have never been studied yet. We found that LDLRAD2 expression was significantly upregulated in GC and closely correlated with poor prognosis in GC patients. Functionally, LDLRAD2 promoted epithelial-mesenchymal transition, migration and invasion, and metastasis of GC cells. Mechanistically, LDLRAD2 interacted with and inhibited Axin1 from binding to cytoplasmic β-catenin, which facilitated the nuclear translocation of β-catenin, thereby activating Wnt/β-catenin pathway. Inhibition of β-catenin activity markedly abolished LDLRAD2-induced migration, invasion and metastasis. Together, these results suggested that LDLRAD2 contributed to invasion and metastasis of GC through activating Wnt/β-catenin pathway. LDLRAD2/ Wnt/β-catenin axis may be a potential therapeutic target for GC treatment.