What is the role of hedgehog signaling in the development and progression of canine cancer?
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Hedgehog (HH) signaling plays a significant role in the development and progression of canine cancer, particularly osteosarcoma (OSA). The aberrant activation of the HH pathway, specifically through the Smoothened (SMO) receptor, contributes to tumorigenesis and progression in both canine and human OSA. In canine OSA cell lines, such as Abrams, D17, and Moresco, dysregulation of HH pathway components like SHH, IHH, SMO, and PTCH1 was observed, leading to increased cell viability and colony-forming ability. Targeting SMO with inhibitors like cyclopamine resulted in decreased cell survival, downregulation of downstream target genes, and increased apoptotic cell death in canine OSA cells, suggesting the potential of the HH/SMO pathway as a novel therapeutic target for canine OSA.
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| Papers (5) | Insight |
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12 Citations | Hedgehog signaling, through GLI transcription factors, plays a crucial role in tumorigenesis across various cancers, including canine cancer, making it a potential target for cancer treatment in dogs. |
| Hedgehog signaling pathway plays crucial roles in cell proliferation, differentiation, and migration in cancer development. It is extensively studied for its involvement in both development and cancer progression. | |
| Not addressed in the paper. | |
| The hedgehog signaling pathway plays a significant role in the development and progression of canine osteosarcoma by influencing cell viability, colony-forming ability, and apoptotic cell death through Smoothened inhibition. | |
| Hedgehog signaling plays a crucial role in normal development and cancer progression by affecting gene regulatory networks. It is a potential target for treating hedgehog-associated diseases, including canine cancer. |
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How does the hedgehog pathway regulate intestinal stem cell function?3 answersThe hedgehog pathway plays a significant role in regulating intestinal stem cell function. It is involved in embryonic development, stem cell regulation, and drug resistance in gastrointestinal cancers. In the intestine, the hedgehog signaling pathway is paracrine, with Hh ligands expressed in the epithelium and signal transduction occurring in the mesenchymal compartment. The epithelial Hh ligands not only regulate mesenchymal cell behaviors but also direct the secretion of additional factors that regulate the epithelial cells themselves. The hedgehog pathway is also involved in maintaining intestinal stem cell homeostasis, with NEDD4 acting as a negative regulator of the Hippo signaling components that control cell proliferation and stem cell homeostasis. Additionally, the hedgehog pathway is involved in orchestrating tissue patterning in the intestine through epithelial-mesenchymal interactions and a negative feedback loop involving Indian hedgehog and bone morphogenetic proteins.
What is the role of iHog in hedgehog signalling in drosophila?5 answersiHog plays a crucial role in Hedgehog (Hh) signaling in Drosophila. It acts as a co-receptor for Hh and forms a receptor complex with Patched to mediate intracellular signaling. iHog also engages in trans-homophilic binding, leading to cytoneme stabilization independent of its role as the Hh receptor. The interaction between iHog and glypicans, such as Dally and Dally-like protein, affects cytoneme behavior and is essential for Hh signaling. The fibronectin III domains of iHog are crucial for its interaction with glypicans and cytoneme stabilization. Additionally, iHog levels are maintained by glypicans, specifically Dally, in cytonemes. The interaction between iHog and glypicans in cytonemes confers the specificity of glypicans for Hh signaling. Overall, iHog plays a dual role in Hh signaling, acting as a co-receptor for Hh and stabilizing cytonemes for efficient Hh transport and reception.
What are the roles of secondary messengers in hedgehog signaling?4 answersSecond messengers play important roles in hedgehog signaling. The primary cilium, which is a signaling compartment, is critical for the activation of the hedgehog pathway. The hedgehog pathway involves the activation of Gli transcription factors, which are proteolytically processed into repressor forms in a protein kinase A (PKA)- and cilium-dependent manner. Calcium signaling also occurs within the primary cilium and is involved in hedgehog signaling. Additionally, cyclic nucleotides such as cAMP and cGMP are important second messengers that are involved in hedgehog signaling. These second messengers share key features that are required for efficient and specific signaling. Overall, the interplay of second messenger systems, such as PKA activation and Gli amplification, is critical for deciphering the role of hedgehog signaling in development and tumorigenesis.
What is hedgehog signaling in drosophila?3 answersHedgehog signaling in Drosophila is a conserved signaling pathway that plays a critical role in embryogenesis, growth, and patterning. It involves the hedgehog ligands (SHH), the Patched (PTCH) receptor, Smoothened (SMO), Suppressor of Fused (SuFu), and GLI transcription factors. The pathway exerts its biological effects through a signaling mechanism that terminates at GLI transcription factors, which mediate various responses as activators or repressors. Aberrant activation of the hedgehog pathway, either ligand-dependent or ligand-independent, has been linked to birth defects and multiple solid cancers. The pathway is regulated by various factors, including the Epidermal Growth Factor (EGF) signaling pathway, adhesion proteins, actin cytoskeleton regulators, and microRNAs. These regulatory mechanisms influence the behavior and range of hedgehog signaling, as well as its gradient formation and robustness.
What are the receptors in hedgehog signalling?3 answersHedgehog signaling involves multiple receptors, including G protein-coupled receptors (GPCRs) such as Mthl5. Additionally, plexins have been identified as novel components of the Hedgehog pathway that promote Hedgehog signaling. Another receptor involved in Hedgehog signaling is Smoothened (SMO), which plays a key role in cardiac development. Furthermore, the astrocyte receptors Patched homolog-1 and Smoothened are important for regulating astrocyte function in the central nervous system. Finally, the common plasma membrane receptor Patched1 is involved in Hedgehog signaling in vertebrates, including in the context of osteoarthritis.