This work, now in press:
-links cell cycle activation with epidermal differentiation.
 |
| An In Vitro Colony of human keratinocytes isolated from a skin biopsy obtained by Dr. E. de Diego at the Paediatric Surgery Department of the Valdecilla Hospital in Santander. |
-reports a skin anti-oncogenic mechanism.
-provides evidence for an oncogene-induced differentiation checkpoint.
Soon in Oncogene and Pubmed.
Oncogene. 2012 Feb 20. doi: 10.1038/onc.2012.22. [Epub ahead of print]
Cyclin E drives human keratinocyte growth into differentiation. Freije A, Ceballos L, Coisy M, Barnes L, Rosa M, De Diego E, Blanchard JM, Gandarillas A.
Source
1] Cell Cycle, Stem Cell Fate and Cancer Laboratory. Institute for Training and Research of the Fundación Marqués de Valdecilla (IFIMAV-FMDV), Santander, Spain [2] Molecular Biology Department of Universidad de Cantabria (UC), Santander, Spain.
Abstract
Human epidermis is continuously exposed to environmental mutagenic hazard and is the most frequent target of human cancer. How the epidermis coordinates proliferation with differentiation to maintain homeostasis, even in hyperproliferative conditions, is unclear. For instance, overactivation of the proto-oncogene MYC in keratinocytes stimulates differentiation. Here we explore the cell cycle regulation as proliferating human keratinocytes commit to terminal differentiation upon loss of anchorage or overactivation of MYC. The S-phase of the cell cycle is deregulated as mitotic regulators are inhibited in the onset of differentiation. Experimental inhibition of mitotic kinase cdk1 or kinases of the mitosis spindle checkpoint Aurora B or Polo-like Kinase, triggered keratinocyte terminal differentiation. Furthermore, hyperactivation of the cell cycle by overexpressing the DNA replication regulator Cyclin E induced mitosis failure and differentiation. Inhibition of Cyclin E by shRNAs attenuated the induction of differentiation by MYC. In addition, we present evidence that Cyclin E induces DNA damage and the p53 pathway. The results provide novel clues for the mechanisms committing proliferative keratinocytes to differentiate, with implications for tissue homeostasis maintenance, HPV amplification and tumorigenesis.Oncogene advance online publication, 20 February 2012; doi:10.1038/onc.2012.22.
PMID:
22349815
[PubMed - as supplied by publisher]
Cyclin E drives human keratinocyte growth into differentiation. Freije A, Ceballos L, Coisy M, Barnes L, Rosa M, De Diego E, Blanchard JM, Gandarillas A.
Source
1] Cell Cycle, Stem Cell Fate and Cancer Laboratory. Institute for Training and Research of the Fundación Marqués de Valdecilla (IFIMAV-FMDV), Santander, Spain [2] Molecular Biology Department of Universidad de Cantabria (UC), Santander, Spain.
Abstract
Human epidermis is continuously exposed to environmental mutagenic hazard and is the most frequent target of human cancer. How the epidermis coordinates proliferation with differentiation to maintain homeostasis, even in hyperproliferative conditions, is unclear. For instance, overactivation of the proto-oncogene MYC in keratinocytes stimulates differentiation. Here we explore the cell cycle regulation as proliferating human keratinocytes commit to terminal differentiation upon loss of anchorage or overactivation of MYC. The S-phase of the cell cycle is deregulated as mitotic regulators are inhibited in the onset of differentiation. Experimental inhibition of mitotic kinase cdk1 or kinases of the mitosis spindle checkpoint Aurora B or Polo-like Kinase, triggered keratinocyte terminal differentiation. Furthermore, hyperactivation of the cell cycle by overexpressing the DNA replication regulator Cyclin E induced mitosis failure and differentiation. Inhibition of Cyclin E by shRNAs attenuated the induction of differentiation by MYC. In addition, we present evidence that Cyclin E induces DNA damage and the p53 pathway. The results provide novel clues for the mechanisms committing proliferative keratinocytes to differentiate, with implications for tissue homeostasis maintenance, HPV amplification and tumorigenesis.Oncogene advance online publication, 20 February 2012; doi:10.1038/onc.2012.22.
PMID:
22349815
[PubMed - as supplied by publisher]
