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Overexpression of dopamine receptor D2 promotes colorectal cancer progression by activating the β-catenin/ZEB1 axis

Authors :
Sehwan Shim
Seung-Sook Lee
Sunhoo Park
Joon Seog Kong
Areumnuri Kim
Min Jung Kim
Hyunjung Lee
Source :
Cancer Science
Publication Year :
2021

Abstract

Colorectal cancer (CRC) is a recurring cancer that is often resistant to conventional therapies and therefore requires the development of molecular‐based therapeutic approaches. Dopamine receptor D2 (DRD2) is associated with the growth of many types of tumors, but its oncogenic role in CRC is unclear. Here, we observed that elevated DRD2 expression was associated with a poor survival rate among patients with CRC. Depletion of DRD2 suppressed CRC cell growth and motility by downregulating β‐catenin/ZEB signaling in vitro and in vivo, whereas overexpression of DRD2 promoted CRC cell progression. Inhibition of DRD2 by the antagonist pimozide inhibited tumor growth and lymph node metastasis in vivo and enhanced the cytotoxic effects of conventional agents in vitro. Taken together, our findings indicate that targeting the DRD2/β‐catenin/ZEB1 signaling axis is a potentially promising therapeutic strategy for patients with CRC.<br />We provided targeting the DRD2/β‐catenin/ZEB1 signaling axis as a potentially promising therapeutic strategy for patients with CRC.

Details

ISSN :
13497006
Volume :
112
Issue :
9
Database :
OpenAIRE
Journal :
Cancer science
Accession number :
edsair.doi.dedup.....83f367ac7fc935200bfe752b6aa83705