Abstract 2469: RCC2 promotes esophageal cancer growth by regulating activity and expression of the Sox2 transcription factor

RCC2 is a protein located in the centrosome, which ensures that cell division proceeds properly. Previous reports show that RCC2 is overexpressed in some cancers and could play a key role in tumor development, but the mechanisms concerning how this occurs are not understood. Further, no evidence exists regarding its role in esophageal cancer. We studied the relevance of RCC2 in esophageal cancer growth and the mechanisms explaining how this process occurs. RCC2 was highly expressed in mouse and human tissues as well as esophageal cancer cell lines, and this overexpression was associated with tumorigenicity. RCC2 promoted cell proliferation, anchorage-independent growth, and migration. These oncogenic effects were accompanied by overexpression of Sox2, an important transcription factor promoting esophageal cancer. RCC2 upregulated and stabilized Sox2 expression by inhibiting proteasome degradation. Likewise, RCC2 increased the transcriptional activity and promoter binding of Sox2. In vivo studies indicated that RCC2 and Sox2 were overexpressed in esophageal tumors compared to normal controls, and this upregulation occurs in the basal cell layer for both proteins. In conditional knockout mice, RCC2 deletion decreased the tumor nodule formation and progression in the esophagus compared with “wild type” mice. PCNA expression, a cell proliferation marker, was also downregulated in RCC2 knockout mice. Overall, our data show for the first time that RCC2 is an important protein for the stabilization and transcriptional activation of Sox2 and further promotion of malignancy in cancer. Citation Format: Ali J. Calderon-Aparicio, Hiroyuki Yamamoto, Humberto de vitto, Tianshun Zhang, Qiushi Wang, Ann M. Bode, Zigang Dong. RCC2 promotes esophageal cancer growth by regulating activity and expression of the Sox2 transcription factor [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2469.