Background: Casein kinase I isoform epsilon (CSNK1E), a gene intricately linked to the circadian clock, has been found to be highly expressed in colorectal cancer (CRC). Elevated expression of CSNK1E correlates with shorter disease-free survival in patients, suggesting a significant, albeit not yet fully understood, role in CRC pathogenesis. The specific molecular mechanisms by which CSNK1E contributes to tumor development and progression remain largely unclear. Given its involvement in key signaling pathways, this study aims to elucidate the functional role of CSNK1E and its underlying mechanisms in CRC, with particular emphasis on its relationship with the Wnt/β-catenin pathway, a cornerstone of CRC oncogenesis.

Methods: CRC cells underwent the intervention on the expression of CSNK1E and dishevelled segment polarity protein 1 (DVL1), a protein interacting with CSNK1E in Wnt/β-catenin signaling. The efficiency of gene modulation was evaluated by qRT-PCR. The interaction between these two genes was validated using Co-immunoprecipitation assays. Phenotypic experiments were subsequently conducted in CRC cells, and Western blot analysis was conducted to assess the status of Wnt/DVL1/β-catenin signaling.

Results: Knockdown of CSNK1E inhibited proliferation (p < 0.01), hindered cell cycle transition from the G1 phase to the S phase (p < 0.05), while inducing apoptosis of CRC cells (p < 0.001). Moreover, CSNK1E was found to bind to DVL1; CSNK1E knockdown significantly decreased the expression of DVL1 and β-catenin in CRC cells (p < 0.05), whereas CSNK1E overexpression exerted an opposite effect (p < 0.05). DVL1 upregulation counteracted the inhibitory effects of CSNK1E knockdown, while DVL1 downregulation offset the promotive effects of CSNK1E overexpression on CRC (p < 0.05).

Conclusion: This study unveils that CSNK1E is a pivotal oncoprotein in CRC. It promotes tumor progression by interacting with and stabilizing DVL1, thereby facilitating the activation of the canonical Wnt/β-catenin signaling pathway. These results highlight the CSNK1E/DVL1 axis as a potential novel therapeutic target for CRC treatment.