The founding member of the hedgehog (HH) family of secreted signaling proteins was identified in 1980 based on mutations that disrupt the body plan of fruit flies. Since then, we have learned that these proteins, and the signaling pathway they triggered, play crucial roles in cell proliferation, differentiation and migration, not only in development, but also in many types of cancers. A unique feature of the vertebrate HH signaling is the essential role for the primary cilium, a singular protrusion from the cell surface that is crucial in orchestrating activities of many cell signaling pathways. Misfiring of the HH pathway underpins the pathology of a large number of clinical manifestations collectively known as ciliopathies, which are caused by disruption of the assembly as well as the integrity of this exquisite microtubule-based structure. The functions of HH and its downstream mediators have also been appreciated in tumor cells as well as in tumor-associated stromal cell types where they exert both pro-tumorigenic and anti-tumorigenic actions, depending on cellular context. The importance of this pathway is further exemplified by the FDA approval of HH/SMO-blockers as a stand-alone anti-cancer therapy. To date, novel regulators and effectors of HH signaling continue to be identified, adding to the complexity of the molecular interaction network.
The goal of this research topic is to reflect on the recent advances and provide perspectives in the molecular mechanisms of HH pathway regulation, the crucial roles of HH signaling in development and pathology, as well as new strategies for treating HH signaling related diseases including cancer. We welcome authors to submit either original studies or review articles on the following topics
1. The molecular mechanisms of HH signal transduction, including regulated ligand release, short and long range gradient formation, ligand/receptor interaction, intracellular signaling including transcription-dependent and transcription-independent responses.
2. The crosstalk between HH signaling and specialized cellular compartments, including the primary cilia in vertebrates, and specialized intracellular compartments in Drosophila and other invertebrate species.
3. New roles of the HH pathway in developmental processes and cancer pathogenesis.
4. New HH pathway-based therapeutic approaches for genetic disorders and cancers.
The founding member of the hedgehog (HH) family of secreted signaling proteins was identified in 1980 based on mutations that disrupt the body plan of fruit flies. Since then, we have learned that these proteins, and the signaling pathway they triggered, play crucial roles in cell proliferation, differentiation and migration, not only in development, but also in many types of cancers. A unique feature of the vertebrate HH signaling is the essential role for the primary cilium, a singular protrusion from the cell surface that is crucial in orchestrating activities of many cell signaling pathways. Misfiring of the HH pathway underpins the pathology of a large number of clinical manifestations collectively known as ciliopathies, which are caused by disruption of the assembly as well as the integrity of this exquisite microtubule-based structure. The functions of HH and its downstream mediators have also been appreciated in tumor cells as well as in tumor-associated stromal cell types where they exert both pro-tumorigenic and anti-tumorigenic actions, depending on cellular context. The importance of this pathway is further exemplified by the FDA approval of HH/SMO-blockers as a stand-alone anti-cancer therapy. To date, novel regulators and effectors of HH signaling continue to be identified, adding to the complexity of the molecular interaction network.
The goal of this research topic is to reflect on the recent advances and provide perspectives in the molecular mechanisms of HH pathway regulation, the crucial roles of HH signaling in development and pathology, as well as new strategies for treating HH signaling related diseases including cancer. We welcome authors to submit either original studies or review articles on the following topics
1. The molecular mechanisms of HH signal transduction, including regulated ligand release, short and long range gradient formation, ligand/receptor interaction, intracellular signaling including transcription-dependent and transcription-independent responses.
2. The crosstalk between HH signaling and specialized cellular compartments, including the primary cilia in vertebrates, and specialized intracellular compartments in Drosophila and other invertebrate species.
3. New roles of the HH pathway in developmental processes and cancer pathogenesis.
4. New HH pathway-based therapeutic approaches for genetic disorders and cancers.
