By Chi-chung Hui, Jin Jiang (auth.), Jingwu Xie (eds.)
Despite major development in our figuring out of melanoma biology, melanoma is still the second one reason behind human mortality. The awesome responses of melanoma sufferers to inhibitors to the hedgehog signaling pathway implies a promising novel method of deal with melanoma. hence, knowing the function of hedgehog signaling in melanoma is significantly vital for novel melanoma therapeutics. The hedgehog pathway, first and foremost stumbled on through Nobel laureates Drs. E. Wieschaus and C. Nusslein-Volhard in Drosophila, is a huge pathway regulating telephone differentiation, tissue polarity, stem mobile upkeep and mobile proliferation. it truly is identified through now that activation of this pathway happens in a number of human melanoma, together with basal telephone carcinomas (BCCs), medulloblastomas, leukemia, gastrointestinal, lung, ovarian, breast and prostate cancers. much more fascinating is the invention and synthesis of particular signaling antagonists for the hedgehog pathway, that have major medical implications in novel melanoma therapeutics. to supply the main up to date details on fresh improvement during this interesting study zone, we've invited specialists in hedgehog signaling box to summarize significant advances made within the previous couple of years on hedgehog signaling mechanisms, activation of the pathway in quite a few human melanoma kinds, capability antagonists for hedgehog signaling inhibition and their medical implications for human melanoma therapy. Authors of the ebook have additionally highlighted present demanding situations in our efforts to translate the elemental biology into health facility. This e-book presents insightful perspectives compatible for graduate scholars, clinical scholars, undergraduate scholars, easy and medical scientists, melanoma sufferers in addition to most people.
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Additional info for Hedgehog Signaling Activation in Human Cancer and Its Clinical Implications
Scube has been described to have a cell non-autonomous requirement in the Hh receiving cells and may thus be involved in the formation of the Hh gradient, like its EGF-like domain containing fly cousin, Shf. In conclusion, several ECM proteins, whether secreted or plasma membrane tethered, control Hh stability and gradient formation in vertebrates, indicating ECM-mediated Hh movement as a common mechanism among different phyla. Hh Uses Multiple Carriers for Its Travels In flies and in vertebrates, Hh acts both at short and long range .
J Biol Chem 273:14037–14045 5. Chamoun Z et al (2001) Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal. Science 293:2080–2084 6. Micchelli CA, The I, Selva E, Mogila V, Perrimon N (2002) Rasp, a putative transmembrane acyltransferase, is required for Hedgehog signaling. Development 129:843–851 7. Amanai K, Jiang J (2001) Distinct roles of Central missing and Dispatched in sending the Hedgehog signal. Development 128:5119–5127 8. Lee JD, Treisman JE (2001) Sightless has homology to transmembrane acyltransferases and is required to generate active Hedgehog protein.
Interestingly, in Drosophila imaginal discs, long cellular protrusions, called cytonemes, are found to extend toward certain morphogen-expressing boundaries . Although no direct evidence for their involvement in Hh signaling has been demonstrated, the morphogen Decapentaplectic (Dpp) is found in cytonemes through which it is directed to its receptor Thickveins in Dpp-responsive cells . Whether Hh uses this mode of transport as a bridge to reach its receptors over several cell diameters is still elusive, but has recently become under intense scrutiny.
Hedgehog Signaling Activation in Human Cancer and Its Clinical Implications by Chi-chung Hui, Jin Jiang (auth.), Jingwu Xie (eds.)