Calcineurin signaling as a negative determinant of keratinocyte cancer stem cell potential and carcinogenesis.


Autoria(s): Dotto G.P.
Data(s)

2011

Resumo

Calcineurin is the only known serine-threonine phosphatase under calcium-calmodulin control and key regulator of the immune system. Treatment of patients with calcineurin-inhibitory drugs like cyclosporin A and FK506 to prevent graft rejection dramatically increases the risk of cutaneous squamous cell carcinoma, which is a major cause of death after organ transplants. Recent evidence indicates that suppression of calcineurin signaling, together with its impact on the immune system, exerts direct tumor-promoting effects in keratinocytes, enhancing cancer stem cell potential. The underlying mechanism involves interruption of a double negative regulatory axis, whereby calcineurin and nuclear factors of activated T-cell signaling inhibits expression of ATF3, a negative regulator of p53. The resulting suppression of keratinocyte cancer cell senescence is of likely clinical significance for the many patients under treatment with calcineurin inhibitors and may be of relevance for other cancer types in which altered calcium-calcineurin signaling plays a role.

Identificador

http://serval.unil.ch/?id=serval:BIB_64972797007B

isbn:1538-7445 (Electronic)

pmid:21406393

doi:10.1158/0008-5472.CAN-10-3750

isiid:000288381300002

Idioma(s)

en

Fonte

Cancer Research, vol. 71, no. 6, pp. 2029-2033

Palavras-Chave #Activating Transcription Factor 3/metabolism; Animals; Calcineurin/metabolism; Carcinoma, Squamous Cell/metabolism; Carcinoma, Squamous Cell/pathology; Humans; Keratinocytes/metabolism; Keratinocytes/pathology; Models, Biological; NFATC Transcription Factors/metabolism; Neoplastic Stem Cells/metabolism; Neoplastic Stem Cells/pathology; Signal Transduction
Tipo

info:eu-repo/semantics/review

article