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.

中文翻译：

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WDR74通过调控Wnt/β-catenin信号通路促进结直肠癌细胞增殖和转移

结肠癌 (CRC) 是一种常见的癌症类型，在世界范围内具有高发病率。由 WD 重复序列组成的蛋白质 74 (WDR74) 以前与肿瘤肿瘤发生有关。然而，其在 CRC 中的作用机制仍不清楚。在这里，我们发现 WDR74 表达在 CRC 组织和细胞中上调。WDR74的下调抑制了CRC细胞的增殖和细胞周期。此外，WDR74 敲低诱导细胞凋亡并抑制细胞转移和侵袭。从机制上讲，WDR74 降低 β-catenin 的磷酸化并诱导核 β-catenin 积累，从而激活 CRC 细胞中的 Wnt/β-catenin 信号通路。进一步研究表明，通过 XAV-939 阻断 Wnt/β-catenin 信号通路可逆转 WDR74 对细胞增殖、迁移、和 HCT116 细胞的侵袭。总体而言，WDR74诱导β-连环蛋白易位至细胞核并激活Wnt/β-连环蛋白，从而促进CRC细胞增殖和转移。总之，WDR74可能是CRC干预的潜在靶点。