DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma

Shitao Zou, Zeng Fu Shang, Biao Liu, Shuyu Zhang, Jinchang Wu, Min Huang, Wei Qun Ding, Jundong Zhou

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

DNA polymerase iota (Pol ι) is an error-prone DNA polymerase involved in translesion DNA synthesis (TLS) that contributes to the accumulation of DNA mutations. We recently showed that Pol ι is overexpressed in human esophageal squamous cell cancer (ESCC) tissues which promotes ESCC' progression. The present study was aimed at investigating the molecular mechanisms by which Pol ι enhances the invasiveness and metastasis of ESCC cells. We found that the expression of Pol ι is significantly higher in ESCCs with lymph node metastasis compared to those without lymph node metastasis. Kaplan-Meier analysis revealed an inverse correlation between Pol ι expression and patient prognosis. The expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two essential regulators of cells' invasiveness, were positively associated with Pol ι expression in ESCC tissues. Ectopic expression of Pol ι enhanced the motility and invasiveness of ESCC cells as evaluated by wound-healing and transwell assays, respectively. A xenograft nude mouse model showed that Pol ι promotes the colonization of ESCC cells in the liver, lung and kidney. Signaling pathway analysis identified the JNK-AP-1 cascade as a mediator of the Pol ι-induced increase in the expression of MMP-2/9 and enhancement of ESCC progression. These data demonstrate the underlying mechanism by which Pol ι promotes ESCC progression, suggesting that Pol ι is a potential novel prognostic biomarker and therapeutic target for ESCC.

Original languageEnglish (US)
Pages (from-to)32274-32285
Number of pages12
JournalOncotarget
Volume7
Issue number22
DOIs
StatePublished - May 31 2016
Externally publishedYes

Keywords

  • DNA polymerase iota
  • Esophageal squamous cell carcinoma
  • JNK-AP-1 cascade
  • Nude mouse
  • Tumor metastasis

ASJC Scopus subject areas

  • Oncology

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