APAF-1 signaling in human melanoma

Research output: Contribution to journalArticle

Abstract

Acquired resistance to mechanisms of programmed cell death is one of the hallmarks of cancer. Human melanoma, in advanced stage, is hardly curable, due to development of several strategies that impair apoptosis induced by the death receptor and the mitochondrial pathways of apoptosis. Among these apoptosis escape strategies, one is based on inactivation of pro-apoptotic factors such as Apoptotic Protease Activating Factor-1 (APAF-1). APAF-1 couples cytochrome c release from the mitochondria to caspase-9 activation and has been considered a central adaptor in the intrinsic pathway of programmed cell death. Inactivation of APAF-1 in human melanoma may impair the mitochondrial pathway of apoptosis induced by chemotherapeutic drugs that activate the p53 pathway, thus contributing to the development of chemoresistance. In-vivo, loss of expression of APAF-1 is associated with tumor progression, suggesting that APAF-1 inactivation may provide a selective survival advantage to neoplastic cells. However, recent results have indicated the existence of APAF-1-independent pathways of caspase activation and apoptosis in normal and neoplastic cells. Moreover, it has been found that expression of APAF-1 is not necessary for the apoptotic response of melanoma cells to different pro-apoptotic drugs. The emerging picture from results obtained in melanoma and other human tumors is that the relevance of the APAF-1 pathway in programmed cell death is cell-context-dependent and related to the specificity of the pro-apoptotic-stimuli.

Original languageEnglish
Pages (from-to)168-179
Number of pages12
JournalCancer Letters
Volume238
Issue number2
DOIs
Publication statusPublished - Jul 18 2006

Fingerprint

Apoptotic Protease-Activating Factor 1
Melanoma
Apoptosis
Cell Death
Neoplasms
Death Domain Receptors
Caspase 9
Prodrugs
Caspases
Cytochromes c
Mitochondria

Keywords

  • APAF-1
  • Apoptosis
  • Melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

APAF-1 signaling in human melanoma. / Anichini, Andrea; Mortarini, Roberta; Sensi, Marialuisa; Zanon, Marina.

In: Cancer Letters, Vol. 238, No. 2, 18.07.2006, p. 168-179.

Research output: Contribution to journalArticle

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