Shi Hubo, Wang Min, Zhao Qianqian, Xu Yihui
Department of Thoracic Surgery, Shandong Public Health Clinical Center, Shandong University, Jinan, Shandong, China.
Medical Research and Laboratory Diagnostic Center, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
IUBMB Life. 2025 Aug;77(8):e70053. doi: 10.1002/iub.70053.
Lung cancer is a severe malignant disease and causes plenty of deaths each year. The survival and prognosis are disappointing for patients with recurrence or metastasis. This is partially due to the lack of mechanisms underlying lung cancer. The ZEB1 gene was reported to promote progression in lung cancer. However, the mechanism of ZEB1 in lung cancer is a puzzle. ZEB1 and WNT7B were expressed more strongly in lung cancer cells. In clinical lung cancer tissues, ZEB1 was also overexpressed compared to the adjacent normal tissues. ZEB1 knockdown (ZEB1-KD) inhibited the activation of Wnt/β-catenin signaling. However, overexpression of WNT7B alleviated this inhibition. Furthermore, ZEB1 was shown to regulate the expression of WNT7B, and WNT7B was the bridge between ZEB1 and Wnt signaling. Cell proliferation and invasion ability were inhibited by ZEB1-KD, which was reversed by WNT7B overexpression. This regulation was supported by the expression patterns of PCNA, E-cadherin, and N-cadherin. In addition, much more cell apoptosis was induced in ZEB1-KD cells treated with Docetaxel compared to that without ZEB1-KD. This induction was reversed when WNT7B was overexpressed. Consistently, the IC50 value in the ZEB1-KD/Docetaxel group was much lower than that in the ZEB1-KD or Docetaxel alone group. In contrast, WNT7B overexpression increased the IC50 value of Docetaxel. In conclusion, ZEB1 positively regulates Wnt/β-catenin signaling in lung cancer and contributes to cancer progression. ZEB1 knockdown increases the efficacy of Docetaxel in lung cancer.
肺癌是一种严重的恶性疾病，每年导致大量死亡。复发或转移患者的生存率和预后令人失望。部分原因是肺癌潜在机制的缺乏。据报道，ZEB1基因可促进肺癌进展。然而，ZEB1在肺癌中的作用机制仍是个谜。ZEB1和WNT7B在肺癌细胞中表达更强。在临床肺癌组织中，与相邻正常组织相比，ZEB1也过表达。ZEB1基因敲低（ZEB1-KD）抑制Wnt/β-连环蛋白信号通路的激活。然而，WNT7B的过表达减轻了这种抑制。此外，ZEB1被证明可调节WNT7B的表达，且WNT7B是ZEB1与Wnt信号之间的桥梁。ZEB1-KD抑制细胞增殖和侵袭能力，而WNT7B的过表达可逆转这种抑制。PCNA、E-钙黏蛋白和N-钙黏蛋白的表达模式支持了这种调节。此外，与未进行ZEB1-KD处理的细胞相比，多西他赛处理的ZEB1-KD细胞诱导了更多的细胞凋亡。当WNT7B过表达时，这种诱导作用被逆转。一致地，ZEB1-KD/多西他赛组的IC50值远低于单独使用ZEB1-KD或多西他赛组。相反，WNT7B的过表达增加了多西他赛的IC50值。总之，ZEB1在肺癌中正向调节Wnt/β-连环蛋白信号通路并促进癌症进展。ZEB1基因敲低可提高多西他赛在肺癌中的疗效。
