Oncogenic B-Raf proto-oncogene, serine/threonine kinase-mediated hedgehog signalling in the pathogenesis and targeted therapy of melanoma

Core Tip

Core Tip: Oncogenic B-Raf proto-oncogene, serine/threonine kinase activates the hedgehog signaling pathway, triggering glioma-associated oncogene homolog (GLI) 1/2 transcription factors that promote melanoma cell invasion and sustain cancer stem cell self-renewal, contributing to the malignancy’s therapeutic resistance. Histone deacetylases 1/2 (HDAC1/2) suppress the acetylation of GLI1/2, facilitating their activation. Inhibiting HDAC1/2 may stabilize GLI proteins in their inactive, acetylated form, offering a novel approach to inhibit melanoma progression. Hedgehog signaling induces HDAC1/2 expression, creating a feedback loop that amplifies GLI-mediated transcription, promoting cancer stem cell renewal. Disrupting this loop could unveil new therapeutic avenues for overcoming melanoma’s resistance to treatment.