Regulator of chromosome condensation 2 (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. Furthermore, no evidence exists regarding its role in
esophageal cancer. We studied the relevance of RCC2 in
esophageal cancer growth and its regulation on Sox2, an important
transcription factor promoting
esophageal cancer. RCC2 was overexpressed in esophageal
tumors compared with normal tissue, and this overexpression was associated with tumorigenicity by increasing cell proliferation, anchorage-independent growth, and migration. These oncogenic effects were accompanied by overexpression of Sox2. RCC2 upregulated and stabilized Sox2 expression and its target genes by inhibiting ubiquitination-mediated
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 with normal tissue, and this upregulation occurs in the esophageal 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.
Proliferating cell nuclear antigen 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
esophageal cancer. IMPLICATIONS: This study shows that RCC2 controls Sox2 expression and transcriptional activity to mediate
esophageal cancer formation.