HECW1 belongs to ubiquitin ligase (E3) HECT family, and is found to be involved in tumorigenesis and tumor progression. However, the function of HECW1 in cervical cancer (CC) remains unknown. Clinical analysis showed that HECW1 is significantly decreased in CC tumor tissues. Ectopic expression of HECW1 suppressed cell growth, promoting cell cycle arrest and apoptosis in CC cells, while downregulation of HECW1 reversed these trends, impeded proliferation and accelerated cell cycle progression of CC cells. Overexpressing of HECW1 reduced mitochondrial membrane potential and the protein expression of voltage-dependent anion channel 1 (VDAC1). In addition, upregulation of HECW1 inhibited nuclear β-catenin accumulation, downregulated β-catenin/TCF/LEF-mediated transcriptional activity and the expression of downstream gene c-Myc, whereas inhibition of HECW1 received opposite results. Further results confirmed HECW1 affects the protein expression of dishevelled-1 (DVL1), a potent activator of Wnt/β‐catenin, and inhibition of HECW1 inhibited the ubiquitination of DVL1, upregulating its expression. Inhibition of DVL1 restrained the promotion effect of HECW1 suppression on cell proliferation. In vivo experiments also verified that HECW1 suppression promoted the tumor formation of CC cells. Summary, we demonstrated that HECW1 inhibits CC cell proliferation and tumor formation by downregulating DVL1 induced Wnt/β‐catenin signaling pathway activation.

HECW1属于泛素连接酶（E3）HECT家族，被发现参与肿瘤的发生和进展。然而，HECW1 在宫颈癌 (CC) 中的功能仍不清楚。临床分析显示HECW1在CC肿瘤组织中显着降低。HECW1的异位表达抑制细胞生长，促进CC细胞的细胞周期停滞和细胞凋亡，而HECW1的下调则逆转这些趋势，阻碍CC细胞的增殖并加速细胞周期进程。HECW1 的过表达会降低线粒体膜电位和电压依赖性阴离子通道 1 (VDAC1) 的蛋白表达。此外，上调HECW1可抑制核β-catenin积累，下调β-catenin/TCF/LEF介导的转录活性和下游基因c-Myc的表达，而抑制HECW1则收到相反的结果。进一步的结果证实 HECW1 影响 Dishevelled-1 (DVL1) 的蛋白表达，DVL1 是 Wnt/β-catenin 的有效激活剂，抑制 HECW1 可以抑制 DVL1 的泛素化，上调其表达。DVL1的抑制抑制了HECW1抑制对细胞增殖的促进作用。体内实验也验证了HECW1抑制促进了CC细胞的肿瘤形成。总之，我们证明 HECW1 通过下调 DVL1 诱导的 Wnt/β-catenin信号通路激活来抑制 CC 细胞增殖和肿瘤形成。