HomeoboxC6 通过调控右侧结肠癌中 DKK1/Wnt/β-catenin 轴促进转移。

HomeoboxC6 promotes metastasis by orchestrating the DKK1/Wnt/β-catenin axis in right-sided colon cancer.

机构信息

Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

出版信息

Cell Death Dis. 2021 Apr 1;12(4):337. doi: 10.1038/s41419-021-03630-x.

Patients with right-sided colon cancer (RCC) generally have a poorer prognosis than those with left-sided colon cancer (LCC). We previously found that homeobox C6 (HOXC6) was the most significantly upregulated gene in RCC compared to LCC. However, it remains unclear whether HOXC6 plays a role in tumor proliferation and metastasis. Our study aimed to explore the potential oncogenic role and the detailed molecular mechanism of HOXC6 in RCC. In this study, HOXC6 was validated to be overexpressed in RCC and associated with poor prognosis. Furthermore, overexpression of HOXC6 promoted the migration and invasion of colon cancer cells through inducing EMT by activating the Wnt/β-catenin signaling pathway and inhibition of DKK1 secretion. Lastly, we preliminary explored the translational effect of HOXC6 and found that silencing of HOXC6 made HCT116 and HT29 cells more sensitive to irinotecan.

右侧结肠癌（RCC）患者的预后一般比左侧结肠癌（LCC）患者差。我们之前发现，与 LCC 相比，同源盒 C6（HOXC6）是 RCC 中上调最显著的基因。然而，HOXC6 是否在肿瘤增殖和转移中发挥作用仍不清楚。本研究旨在探讨 HOXC6 在 RCC 中的潜在致癌作用及其详细的分子机制。在这项研究中，验证了 HOXC6 在 RCC 中过度表达，并与不良预后相关。此外，通过激活 Wnt/β-catenin 信号通路和抑制 DKK1 分泌诱导 EMT，HOXC6 的过表达促进了结肠癌细胞的迁移和侵袭。最后，我们初步探讨了 HOXC6 的翻译效应，发现沉默 HOXC6 使 HCT116 和 HT29 细胞对伊立替康更敏感。