Hepatocellular carcinoma (HCC) is one of the most fatal cancers worldwide. In this article, we show that expression of abnormal spindle-like microcephaly-associated protein (ASPM) is up-regulated in liver cancer samples, and this up-regulation is significantly associated with tumor aggressiveness and reduced survival times of patients. Down-regulation of ASPM expression inhibits the proliferation, invasion, migration and epithelial-to-mesenchymal transition of HCC cells in vitro and inhibits tumor formation in nude mice. ASPM interacts with disheveled-2 (Dvl2) and antagonizes autophagy-mediated Dvl2 degradation by weakening the functional interaction between Dvl2 and the lipidated form of microtubule-associated proteins 1A/1B light chain 3A (LC3II), thereby increasing Dvl2 protein abundance and leading to Wnt/β-catenin signaling activation in HCC cells. Thus, our results define ASPM as a novel oncoprotein in HCC and indicate that disruption of the Wnt–ASPM–Dvl2–β-catenin signaling axis might have potential clinical value.

中文翻译：

---

ASPM通过拮抗自噬介导的Dvl2降解激活Wnt/β-catenin信号促进肝细胞癌进展

肝细胞癌（HCC）是全球最致命的癌症之一。在本文中，我们发现异常纺锤样小头畸形相关蛋白 (ASPM) 在肝癌样本中的表达上调，这种上调与肿瘤侵袭性和患者生存时间缩短显着相关。体外下调ASPM表达抑制HCC细胞的增殖、侵袭、迁移和上皮间质转化并抑制裸鼠的肿瘤形成。ASPM 与 diseveled-2 (Dvl2) 相互作用，并通过削弱 Dvl2 与脂化形式的微管相关蛋白 1A/1B 轻链 3A (LC3II) 之间的功能相互作用来拮抗自噬介导的 Dvl2 降解，从而增加 Dvl2 蛋白丰度并导致HCC细胞中的Wnt/β-连环蛋白信号激活。因此，我们的结果将 ASPM 定义为 HCC 中的一种新型癌蛋白，并表明 Wnt-ASPM-Dvl2-β-连环蛋白信号轴的破坏可能具有潜在的临床价值。