Tumor necrosis factor-alpha blocks apoptosis in melanoma cells when BRAF signaling is inhibited.

The protein kinase BRAF, a component of the RAS/RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway, regulates cell fate in response to extracellular signals. Activating mutations in BRAF occur in approximately 70% of human melanomas. The active proteins stimulate constitutive pathway signaling, proliferation, and survival.

The role of B-RAF in melanoma.

Melanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. If detected early, it is easily treated by surgical excision. However, once melanoma metastasises it is notoriously resistant to existing therapies and for many patients the outlook is dismal.

p16/cyclin-dependent kinase inhibitor 2A deficiency in human melanocyte senescence, apoptosis, and immortalization: possible implications for melanoma progression.

Background: The melanoma susceptibility locus cyclin-dependent kinase inhibitor 2A encodes two unrelated cell growth inhibitors, p16 and alternative reading frame (ARF). In fibroblasts, both proteins are implicated in cellular senescence, a key barrier to tumor development. The p16 coding sequence is more often mutated in melanoma families than is the ARF sequence.