title: DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma.
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.
authors.affiliation: Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215001, P.R. China.
authors.forename: Shitao
authors.initials: S
authors.lastname: Zou
authors.affiliation: School 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.
authors.forename: Zeng-Fu
authors.initials: ZF
authors.lastname: Shang
authors.affiliation: Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215001, P.R. China.
authors.forename: Biao
authors.initials: B
authors.lastname: Liu
authors.affiliation: School 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.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215001, P.R. China.
authors.forename: Jinchang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215001, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Pathology, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.
authors.forename: Wei-Qun
authors.initials: WQ
authors.lastname: Ding
authors.affiliation: Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215001, P.R. China.
authors.forename: Jundong
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011379:Prognosis; D015398:Signal Transduction; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D000094769:DNA Polymerase iota
chemical_list: D014408:Biomarkers, Tumor; D018808:Transcription Factor AP-1; D048031:JNK Mitogen-Activated Protein Kinases; D004259:DNA-Directed DNA Polymerase; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D000094769:DNA Polymerase iota
keywords: DNA polymerase iota; JNK-AP-1 cascade; esophageal squamous cell carcinoma; nude mouse; tumor metastasis