Abstract
Colon cancer (CRC) is a common type of cancer and has a high incidence worldwide. Protein 74 (WDR74), which consists of the WD repetition sequence, has been previously associated with tumor tumorigenesis. However, its mechanism of action in CRC remains unclear. Here, we found that WDR74 expression was upregulated in CRC tissues and cells. Downregulation of WDR74 repressed the proliferation and cell cycles in CRC cells. In addition, WDR74 knockdown induced cell apoptosis and suppressed both cell metastasis and invasion. Mechanistically, WDR74 decreased the phosphorylation of β-catenin and induced nuclear β-catenin accumulation, activating the Wnt/β-catenin signaling pathway in CRC cells. Further investigation showed that blocking the Wnt/β-catenin signaling pathway by XAV-939 reversed the effects of WDR74 on cell proliferation, migration, and invasion in HCT116 cells. Overall, WDR74 induced β-catenin translocation to the nucleus and activated the Wnt/β-Catenin, thus facilitated CRC cell proliferation and metastasis. In summary, WDR74 could be a potential target for the intervention of CRC.
Highlights
As one of the most common gastrointestinal tumors in China and worldwide, colon cancer (CRC) has a highThe Wnt/β-catenin signaling has been highly conserved in evolution and can play a role in the growth, development, tissue regeneration, occurrence of tumors and diseases, and many other physiological and pathological processes [5]
3.1 worldwide. Protein 74 (WDR74) was upregulated in CRC cells expression of WDR74 was consistently upregulated in CRC cell lines compared to controls (Figure 1b and c)
Previous studies have shown that WDR74 acts as a coactivator in TGF-β signaling and is involved in a variety of biological processes including cell proliferation, cell differentiation, cell signaling, and gene transcription [15]
Summary
The Wnt/β-catenin signaling has been highly conserved in evolution and can play a role in the growth, development, tissue regeneration, occurrence of tumors and diseases, and many other physiological and pathological processes [5]. Most cases of CRC are caused by mutations in components of the Wnt signaling mutations [6]. Dysregulation of the Wnt/β-catenin signaling pathway has been shown to be related to the metastasis in CRC [8]. Oncogenic mutations in CRC result in the stabilization and translocation of β-catenin to the nucleus and induced its downstream genes expression, such as c-Myc, CCND1, and MMP-7, which contributed to cell proliferation, survival, and metastasis [9,10]. Wnt/β-catenin signaling plays a critical role in the development and progression of CRC
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