Prdx1 promotes the loss of primary cilia in esophageal squamous cell carcinoma

Qiongzhen Chen,Jinmeng Li,Yu Liu,Fanghua Gong,Xiaoning Yang,Junfeng Ma

doi:10.1186/s12885-020-06898-y

Abstract

BackgroundLoss 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.MethodsInhibiting 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.ResultsIn 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.ConclusionsThese results suggest that Prdx1 is a novel regulator of primary cilia formation in ESCC cells.

Highlights

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
The experimental cells were divided into seven groups, normal EC9706 cells, EC9706 cells transfected with shPrdx1 lentivirus, EC9706 cells transfected with negative control lentivirus, EC9706 cells transfected with OE-Peroxiredoxin 1 (Prdx1) lentivirus (OEPrdx1), EC9706 cells transfected with corresponding negative control lentivirus (OE-Control), EC9706 cells treated with Tripolin A (EC9706 + Tripolin A), and EC9706 cells transfected with OE-Prdx1 lentivirus and treated with Tripolin A (OE-Prdx1 + Tripolin A)
Inhibition of prdx1 restored primary cilia and suppressed tumor invasion In order to study the effect of inhibition of Prdx1 on cilia and cell function, we used gene chip detection followed by experiments in cells to verify the findings

Summary

Introduction

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. The primary cilium is an antenna-like organelle present on the surface of most types of mammals, with an extracellular signal transduction function that regulates cell growth and development. Cilium disassembly is closely associated with cell cycle progression and external signal transduction [1,2,3]. Recent studies have shown that cilia are closely associated with tumorigenesis [7,8,9], and primary cilia are disassembled or lost in many tumor tissues, including esophageal squamous. Several studies have shown that Prdx is highly expressed in

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Conclusion