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.
Highlights
Gastric cancer (GC), a lethal disease, prevails worldwide [1]
We found that mRNA expression of LDLRAD2 was significantly upregulated in GC samples compared with normal samples (Figure 1A) and it was inversely correlated with overall survival (Figure 1B) and disease-free survival (Figure 1C) of GC patients
Our western blotting analysis showed that LDLRAD2 expression was significantly upregulated in GC tissues (Figure 1F) and GC cell lines compared with their counterparts (Figure 1G)
Summary
GC is the second most common cancer and the second leading cause of cancerrelated deaths [2, 3]. GC patients diagnosed at an advanced stage suffer from distant invasion and metastasis, which largely increased cancer-associated deaths [4, 5]. As a new strategy, has been expected to a novel promising strategy to treat cancer patients [8, 9]. It is imperative to further elucidate the molecular mechanisms underlying GC invasion and www.aging-us.com metastasis fully so as to identify novel effective therapeutic targets [13]
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