2016
Monday September 19th
15:00 pm - 16:00 pm
Conférence

Regulation of Wnt secretion: Biology and Therapy

Conférence en English
Information

Wnt signaling is essential in both development and the homeostasis of several adult tissues, and its dysregulation is implicated in multiple cancers. The role of Wnts in the adult stem cell niche can be defined by genetic and pharmacologic manipulation of Wnt secretion. Recent identification of genetic mutations in upstream regulators of Wnt sensitivity defines a subset of cancers that may respond to treatment with upstream Wnt inhibitors. Wnt secretion can be blocked by genetic ablation or small molecule inhibition of the membrane bound O-acyl transferase PORCN that is required for the post-translational modification of all Wnts. Consistent with a central role of Wnt signaling in regulation of cancer gene expression, inhibition of PORCN causes a marked remodeling of the transcriptome. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers.Wnt signaling is essential in both development and the homeostasis of several adult tissues, and its dysregulation is implicated in multiple cancers. The role of Wnts in the adult stem cell niche can be defined by genetic and pharmacologic manipulation of Wnt secretion. Recent identification of genetic mutations in upstream regulators of Wnt sensitivity defines a subset of cancers that may respond to treatment with upstream Wnt inhibitors. Wnt secretion can be blocked by genetic ablation or small molecule inhibition of the membrane bound O-acyl transferase PORCN that is required for the post-translational modification of all Wnts. Consistent with a central role of Wnt signaling in regulation of cancer gene expression, inhibition of PORCN causes a marked remodeling of the transcriptome. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers.