engleski

Epigenetic regulation of the Hedgehog-Gli signaling pathway in cancer

The term epigenetics refers to the modulation of gene expression caused by means other than changes in the DNA sequence. Alongside with genetic alterations, epigenetic changes can also be considered a hallmark of cancer. Epigenetic silencing of tumor suppressors can serve as one of the hits in the Knudson’s two hit model of tumor initiation when in conjunction with genetic mutations or deletions. Also, loss of methylation can be implicated in tumorigenesis by activating normally silent regions of the genome. The Hedgehog-Gli signaling pathway has been highly conserved through evolution and plays a crucial role during embryonic development from Drosophila to humans. Malfunction of the Hh-Gli signaling pathway in humans has first been observed in Gorlin syndrome, characterized by developmental malformations and cancer susceptibility. In the last decades aberrant activation of the Hh-Gli signaling pathway has been implicated in various sporadic tumors, both benign and malignant ones. Genetic alterations of the Hh-Gli signaling pathway components and their implication in the development of various types of cancer and developmental malformations are well known. In the last few years it has become obvious that epigenetic changes also play a crucial role in the regulation of this pathway.

Hedgehog signaling; epigenetics; DNA methylation

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