ERCC6L promotes cell growth and metastasis in gastric cancer through activating NF-κB signaling.

Dehu Chen,Gan Cao,Qinghong Liu

doi:10.18632/aging.203387

Abstract

ERCC6L has been reported to act as a potential oncogenic protein in various cancers. However, the role of ERCC6L in the progression of gastric cancer (GC) remains to be elucidated. Herein, we aimed to assess the clinical significance, the role, and the underlying mechanism of ERCC6L in GC progression. In this study, the mRNA and protein expression levels of ERCC6L were measured in GC specimens by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry, and its clinical significance was assessed. The effect of ERCC6L overexpression or knockdown on GC cell growth, migration, and invasion was explored by functional experiments. Notably, the possible mechanisms underlying the action of ERCC6L were also investigated. We found that ERCC6L was upregulated in GC tissues, and its expression was associated with tumor size, clinical stage, and poor prognosis in GC patients. Besides, ERCC6L facilitated GC cell proliferation and metastasis in vitro and in vivo. Mechanically, ERCC6L modulated GC cell behavior via activation of NF-κB signaling. Our results indicated that ERCC6L played a critical role in GC progression and metastasis. In addition, ERCC6L promoted GC cell growth and metastasis via activation of NF-κB signaling, thus possibly providing a target for GC.

Highlights

IntroductionDespite advances in the development of surgery and chemotherapy in recent years, the prognosis of gastric cancer (GC) patients remains dissatisfactory as a result of recurrence and metastasis rates [3]
Worldwide, gastric cancer (GC) is one of the most common malignant tumors [1,2]
We found that ERCC6L was upregulated in GC tissues, and its expression was associated with tumor size, clinical stage, and poor prognosis in GC patients

Summary

Introduction

Despite advances in the development of surgery and chemotherapy in recent years, the prognosis of GC patients remains dissatisfactory as a result of recurrence and metastasis rates [3]. Growing evidence has revealed that epithelial-mesenchymal transition (EMT) is a fundamental process of tumor initiation and progression. During EMT, epithelial cells lose their intercellular junction, reprogram gene expression and undergo a substantial change in signalling programme; this switch modifies the cell shape to promote motility and invasion [4]. A hallmark of EMT is E-cadherin level downregulation and N-cadherin level upregulation. These changes in gene expression are regulated by transcription factors as well as an intricate network of signalling pathways, including TGF-β, JAK-STAT, PI3K/Akt, MAPK, and NF-κB [5]

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