Background
Colorectal cancer (CRC) is a common disease threatening human lives worldwide, and vitamin D receptor (VDR) contributes protective roles in this disease. However, the molecular mechanisms underlying VDR protection in CRC progression require further investigation.
Conclusions
This study indicated that VDR protected against CRC disease in humans by inhibiting Wnt/β-catenin signalling to control cancer cell invasion and apoptosis, providing new evidence to explore VDR biomarkers or agonists for CRC patient diagnosis and treatment.
Methods
In this study, we statistically analyzed the relationship between VDR expression and CRC development in patients and detected invasion and apoptosis in CRC cells with VDR overexpression and interference. We also detected the expression of key genes involved in Wnt/β-catenin signalling (β-catenin, lymphoid enhancer factor (LEF)-1 and cyclin D1) in SW480 cells and nude mice injected with VDR-overexpressing SW480 cells and observed tumour development. Additionally, we performed Co-immunoprecipitation (Co-IP) and glutathione-S-transferase (GST) pull-down assays to identify the protein interactions of VDR with β-catenin, dual luciferase (LUC) and chromatin immunoprecipitation (ChIP) to detect the activation of LEF-1 by VDR.
Results
The VDR level was closely related to the development and prognosis of CRC patients. VDR overexpression inhibited invasion but promoted apoptosis in cancer cells. β-catenin shRNA contributed oppositely to cancer cell activity with VDR shRNA. Additionally, VDR interacted with β-catenin at the protein level and blocked its nuclear accumulation. VDR regulated the expression of β-catenin, cyclin D1 and LEF-1 and directly activated LEF-1 transcription in vitro. Furthermore, nude mice injected with VDR-overexpressing SW480 cells revealed suppression of tumour growth and decreased expression of β-catenin, cyclin D1 and LEF-1. Conclusions: This study indicated that VDR protected against CRC disease in humans by inhibiting Wnt/β-catenin signalling to control cancer cell invasion and apoptosis, providing new evidence to explore VDR biomarkers or agonists for CRC patient diagnosis and treatment.