The role of Cdc6 in cancer progression
CDC6 acts as a prototypical oncogenic stimulus operating in a bimodal manner (1-4): i) triggering replication stress, fueling genomic instability (1,2,3), ii) functioning as a transcriptional repressor by switching off the INK4A/ARF and CDH1 (E-cadherin) loci, disrupting cell cycle progression and cell-to-cell communication (3,4).
1) Karakaidos et al. Overexpression of the replication licensing regulators hCdt1 and hCdc6 characterizes a subset of non-small-cell lung carcinomas: synergistic effect with mutant p53 on tumor growth and chromosomal instability--evidence of E2F-1 transcriptional control over hCdt1. Am J Pathol 2004, 165(4): 1351-65.
2) Liontos et al. Deregulated overexpression of hCdt1 and hCdc6 promotes malignant behavior. Cancer Res 2007, 67(22): 10899-909.
3) Sideridou et al. Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins. J Cell Biol 2011, 195(7): 1123-40.
4) Petrakis et al. Cdc6: a multi-functional molecular switch with critical role in carcinogenesis. Transcription 2012, 3(3): 124-9.
