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Cetuximab inhibits colorectal cancer development through inactivating the Wnt/β-catenin pathway and modulating PLCB3 expression

Authors :
Xiaohong Zhang
Wenming Zhou
Chenqu Wu
Jun Jiang
Qianqian Guo
Li Feng
Xun Cheng
Xingxing Zhang
Source :
Scientific Reports, Vol 14, Iss 1, Pp 1-12 (2024)
Publication Year :
2024
Publisher :
Nature Portfolio, 2024.

Abstract

Abstract Colorectal cancer (CRC) often necessitates cetuximab (an EGFR-targeting monoclonal antibody) for treatment. Despite its clinical utility, the specific operative mechanism of cetuximab remains elusive. This research investigated the influence of PLCB3, a potential CRC oncogene, on cetuximab treatment. We extracted differentially expressed genes from the GSE140973, the overlapping genes combined with 151 Wnt/β-Catenin signaling pathway-related genes were identified. Then, we conducted bioinformatics analysis to pinpoint the hub gene. Subsequently, we investigated the clinical expression characteristics of this hub gene, through cell experimental, scrutinized the impact of cetuximab and PLCB3 on CRC cellular progression. The study identified 26 overlapping genes. High expression of PLCB3, correlated with poorer prognosis. PLCB3 emerged as a significant oncogene associated with patient prognosis. In vitro tests revealed that cetuximab exerted a cytotoxic effect on CRC cells, with PLCB3 knockdown inhibiting CRC cell progression. Furthermore, cetuximab treatment led to a reduction in both β-catenin and PLCB3 expression, while simultaneously augmenting E-cadherin expression. These findings revealed PLCB3 promoted cetuximab inhibition on Wnt/β-catenin signaling. Finally, simultaneous application of cetuximab with a Wnt activator (IM12) and PLCB3 demonstrated inhibited CRC proliferation, migration, and invasion. The study emphasized the pivotal role of PLCB3 in CRC and its potential to enhance the efficacy of cetuximab treatment. Furthermore, cetuximab suppressed Wnt/β-catenin pathway to modulate PLCB3 expression, thus inhibiting colorectal cancer progression. This study offered fresh perspectives on cetuximab mechanism in CRC.

Details

Language :
English
ISSN :
20452322
Volume :
14
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.b4fc344682f547fd928ce0d39c233064
Document Type :
article
Full Text :
https://doi.org/10.1038/s41598-024-59676-2