Abstract 707: High expression of Pol é promotes invasion and metastases in esophageal squamous cell carcinoma

Abstract

Abstract . DNA polymerase iota (Pol iota) is an error-prone DNA polymerase involved in translesion DNA synthesis (TLS) that may play a significant role in the accumulation of DNA mutations. Our previous studies identified the elevated expression of Pol iota in human esophageal squamous cell cancer (ESCC) tissues and revealed that Pol iota contributes to ESCCs’ progression. The present study aimed to investigate the molecular mechanism by which Pol iota enhances the invasiveness and metastasis of ESCC cells. We found that the expression of Pol iota was higher in ESCCs with lymph node metastasis compared to those without lymph node metastasis. Kaplan-Meier analysis revealed a negative correlation between the expression of Pol iota and patients’ prognosis. Furthermore, the expression of matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase-9(MMP-9), both being essential regulators for cells invasion, were associated with that of Pol iota in ESCCs tissue samples. The wound healing and transwells assay revealed that over-expression of Pol iota enhances motility and invasiveness of ESCC cells. In vivo, up-regulation of Pol iota promoted the colonization of ESCC cells in the liver, lung and kidney. Signaling pathway analysis showed that Pol iota induces the expression of MMP-2/9 and enhances the ESCCs progression via JNK-AP-1 cascade. Altogether, our finding demonstrated the underlying mechanism by which Pol iota promotes ESCCs’ development. Citation Format: Shitao Zou, Jinchang Wu, Wei-Qun Ding, Jundong Zhou. High expression of Pol é promotes invasion and metastases in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 707.