Oncotarget

Research Papers:

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 and Jundong Zhou

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Oncotarget. 2016; 7:32274-32285. https://doi.org/10.18632/oncotarget.8580

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Abstract

Shitao Zou1,*, Zeng-Fu Shang2,*, Biao Liu1, Shuyu Zhang2, Jinchang Wu1, Min Huang1, Wei-Qun Ding3, Jundong Zhou1

1Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215001, P.R. China

2School of Radiation Medicine and Protection, Medical College of Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, Jiangsu, 215123, P.R. China

3Department of Pathology, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA

*These authors have contributed equally to this work

Correspondence to:

Jundong Zhou, email: zhoujundong330@163.com

Min Huang, email: szhuangmin@163.com

Jinchang Wu, email: wjinchang@sina.com

Keywords: esophageal squamous cell carcinoma, DNA polymerase iota, tumor metastasis, JNK-AP-1 cascade, nude mouse

Received: February 03, 2016     Accepted: March 28, 2016     Published: April 4, 2016

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.


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