Melanoma survival strategies: the intrinsic apoptotic pathway: upstream and downstream regulators

ABSTRACT

Apoptotic cell death is involved in development and tissue homeostasis in numerous organisms, and changes in the apoptotic pathways are associated with many diseases, including cancer. The first evidence for an association between apoptosis and cancer was the discovery that the oncogene bcl-2 was involved in cell survival in lymphoma. Since then, alterations in the expression of genes that participate in cell survival pathways and resistance to apoptosis have become a hallmark of cancer. A failure to trigger apoptosis properly is an essential requirement during tumor progression and contributes to tumor resistance to radioor chemotherapy. Melanoma, one of the most aggressive cancers, is characterized by an elevated capacity to metastasize and by a high resistance to drugs. The strategies used by melanoma cells to avoid apoptosis often differ from those in other cancer cells. For example, in contrast to many tumors that frequently show a loss of p53 expression, melanoma maintains p53 expression but alters the p53 pathways. In this review, we summarize various aspects of melanocyte biology and consider the genetic alterations exploited by melanoma cells to escape apoptosis. We also discuss recent findings that have extended our understanding of the resistance of melanocytes to apoptosis during tumor progression.