College of Life and Environmental Science, Wenzhou University, Wenzhou, China.
School of Pharmacy, Wenzhou Medical University, Wenzhou, China.
BMC Cancer. 2020 May 1;20(1):372. doi: 10.1186/s12885-020-06898-y.
Loss of primary cilia is frequently observed in tumor cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction, the inability to exit the cell cycle, and promotion of tumor cell invasion. Primary cilia loss also occurs in esophageal squamous cell carcinoma (ESCC) cells, but the molecular mechanisms that explain how ESCC cells lose primary cilia remain poorly understood.
Inhibiting the expression of Prdx1 in the ESCC cells to detect the up-regulated genes related to cilium regeneration and down-regulated genes related to cilium disassembly by Gene chip. And, mice and cell experiments were carried to confirm the role of the HEF1-Aurora A-HDAC6 signaling axis in ESCC.
In this study, we found that silencing Peroxiredoxin 1 (Prdx1) restores primary cilia formation, and over-expressing Prdx1 induces primary cilia loss in ESCC cells. We also showed that the expression of Prdx1 regulates the action of the HEF1-Aurora A-HDAC6 signaling axis to promote the disassembly of primary cilia, and suppression of Prdx1 results in decreased tumor formation and tumor mass volume in vivo.
These results suggest that Prdx1 is a novel regulator of primary cilia formation in ESCC cells.
肿瘤细胞中经常观察到初级纤毛的缺失，这表明这种细胞器的缺失可能通过异常的信号转导、无法退出细胞周期以及促进肿瘤细胞侵袭来促进肿瘤发生。食管鳞状细胞癌（ESCC）细胞中也会发生初级纤毛缺失，但解释 ESCC 细胞如何失去初级纤毛的分子机制仍知之甚少。
通过基因芯片检测抑制 ESCC 细胞中 Prdx1 表达后与纤毛再生相关的上调基因和与纤毛解体相关的下调基因。并通过小鼠和细胞实验证实了 HEF1-Aurora A-HDAC6 信号轴在 ESCC 中的作用。
本研究发现，沉默过氧化物酶 1（Prdx1）可恢复初级纤毛的形成，而过表达 Prdx1 可诱导 ESCC 细胞中初级纤毛的缺失。我们还表明，Prdx1 的表达调节 HEF1-Aurora A-HDAC6 信号轴的作用，以促进初级纤毛的解体，抑制 Prdx1 可导致体内肿瘤形成和肿瘤体积减少。
这些结果表明 Prdx1 是 ESCC 细胞中初级纤毛形成的新型调节因子。
