A state of stochastic cancer stemness through the CDK1-SOX2 axis
Metrics: PDF 335 views | Full Text 496 views | ?
Dinoop Ravindran Menon1 and Mayumi Fujita1,2,3
1 Department of Dermatology, University of Colorado Denver, Aurora, CO, USA
2 Denver VA Medical Center, Denver, CO, USA
3 Department of Immunology and Microbiology, University of Colorado Denver, Aurora, CO, USA
Mayumi Fujita, email: firstname.lastname@example.org
Keywords: cancer stemness; melanoma; immune evasion; CDK1; SOX2
Received: January 25, 2019 Accepted: February 03, 2019 Published: April 05, 2019
The concept of cancer stemness has undergone a paradigm shift during the last decade where there is wider acceptance of the idea that stemness in cancer is a more dynamic and plastic phenomenon than previously thought. However, we have yet to understand the mechanisms on how this stochastic plasticity arises and is maintained. Recently, we have shown that CDK1 plays a critical role in stochastic stemness and tumor initiation potential through regulating SOX2 phosphorylation in multiple cancer types. The phosphorylation of SOX2 affects its nuclear localization, thereby determining the transcriptional fate of its downstream targets. We have also validated the significance of these findings using clinical samples by demonstrating that CDK1high tumor samples displayed upregulation of MYC target genes, which were reported to overlap with SOX2 targets. In the current article, we further discuss the possibility of a closed, feed-forward loop between SOX2 and CDK1 through a long non-coding RNA, CCAT1, which would explain the sustained activation of this loop. Despite the extensive investigation of the cancer stemness as a cause of drug resistance, its role in immune evasion still requires further understanding, and hence, in this article, we further discuss the possibility of this CDK1-SOX2 axis contributing to immune resistance through modulating cell-to-cell interaction directly or indirectly in the tumor microenvironment.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.