RAD18 promotes the migration and invasion of esophageal squamous cell cancer via the JNK-MMPs pathway

Shitao Zou, Jianlong Yang, Jiaming Guo, Ye Su, Chao He, Jinchang Wu, Lan Yu, Wei Qun Ding, Jundong Zhou

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

As a key regulator of DNA translesion synthesis (TLS) pathway, RAD18 is error-prone and contributes to the accumulation of DNA mutations. We have recently shown that RAD18 is overexpressed in human esophageal squamous cell cancer (ESCC) and acts to promote ESCC progression. The current study aims to understand the molecular mechanism by which RAD18 enhances the invasiveness and metastasis of ESCC cells. We found that RAD18 expression is markedly higher in high T stage ESCCs compared to low T stage groups. Kaplan-Meier analysis showed an inverse correlation between RAD18 expression and patient prognosis. The expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two vital mediators of cell invasion and proliferation, positively correlated with RAD18 expression in ESCC tissues. Ectopic expression of RAD18 enhanced the motility and invasiveness of ESCC cells as evaluated by wound-healing assays and transwell assays. A xenograft nude mouse model showed that RAD18 promoted the colonization of ESCC cells in vivo. Signaling pathway analysis identified the JNK-MMP cascade as a mediator of RAD18-induced enhancement of ESCC progression. These data demonstrate the underlying mechanism by which RAD18 promotes ESCC progression, suggesting that RAD18 is a promising novel prognostic biomarker and therapeutic target against ESCC.

Original languageEnglish (US)
Pages (from-to)65-74
Number of pages10
JournalCancer Letters
Volume417
DOIs
StatePublished - Mar 28 2018
Externally publishedYes

Fingerprint

Squamous Cell Neoplasms
MAP Kinase Signaling System
Esophageal Neoplasms
Matrix Metalloproteinases
Matrix Metalloproteinase 2
DNA
Matrix Metalloproteinase 9
Kaplan-Meier Estimate
Heterografts
Nude Mice
Wound Healing
Biomarkers
Cell Proliferation
Neoplasm Metastasis

Keywords

  • c-Jun N-Terminal kinase,
  • DNA translesion synthesis
  • Esophageal squamous cell cancer
  • Metastasis
  • RAD18

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

RAD18 promotes the migration and invasion of esophageal squamous cell cancer via the JNK-MMPs pathway. / Zou, Shitao; Yang, Jianlong; Guo, Jiaming; Su, Ye; He, Chao; Wu, Jinchang; Yu, Lan; Ding, Wei Qun; Zhou, Jundong.

In: Cancer Letters, Vol. 417, 28.03.2018, p. 65-74.

Research output: Contribution to journalArticle

Zou, Shitao ; Yang, Jianlong ; Guo, Jiaming ; Su, Ye ; He, Chao ; Wu, Jinchang ; Yu, Lan ; Ding, Wei Qun ; Zhou, Jundong. / RAD18 promotes the migration and invasion of esophageal squamous cell cancer via the JNK-MMPs pathway. In: Cancer Letters. 2018 ; Vol. 417. pp. 65-74.
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AU - Ding, Wei Qun

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