mTORC1-mediated inhibition of 4EBP1 is essential for Hedgehog (HH) signaling and can be targeted to suppress HH-driven medulloblastoma
نویسندگان
چکیده
Department of Developmental Neurobiology and Department of Pathology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, 47 bld de l'hôpital, Paris 13, France. Department of Pathology, The Johns Hopkins University School of Medicine, Ross Building 558, 720 Rutland Ave, Baltimore, MD 21205, USA.
منابع مشابه
Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway.
Uncontrolled Hedgehog (Hh) signaling is the cause of several malignancies, including the pediatric cancer medulloblastoma, a neuroectodermal tumor affecting the cerebellum. Despite the development of potent Hh pathway antagonists, medulloblastoma drug resistance is still an unresolved issue that requires the identification of novel drug targets. Following up on our observation that histone deac...
متن کاملClinical implications of hedgehog signaling pathway inhibitors
Hedgehog was first described in Drosophila melanogaster by the Nobel laureates Eric Wieschaus and Christiane Nüsslein-Volhard. The hedgehog (Hh) pathway is a major regulator of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer was established through studies of a rare familial disease, Gorlin syndrome, in 19...
متن کاملPhosphodiesterase 4D acts downstream of Neuropilin to control Hedgehog signal transduction and the growth of medulloblastoma
Alterations in Hedgehog (Hh) signaling lead to birth defects and cancers including medulloblastoma, the most common pediatric brain tumor. Although inhibitors targeting the membrane protein Smoothened suppress Hh signaling, acquired drug resistance and tumor relapse call for additional therapeutic targets. Here we show that phosphodiesterase 4D (PDE4D) acts downstream of Neuropilins to control ...
متن کاملRepurposing the antihelmintic mebendazole as a hedgehog inhibitor.
The hedgehog (Hh) signaling pathway is activated in many types of cancer and therefore presents an attractive target for new anticancer agents. Here, we show that mebendazole, a benzamidazole with a long history of safe use against nematode infestations and hydatid disease, potently inhibited Hh signaling and slowed the growth of Hh-driven human medulloblastoma cells at clinically attainable co...
متن کاملThe energy sensor AMPK regulates Hedgehog signaling in human cells through a unique Gli1 metabolic checkpoint
Hedgehog signaling controls proliferation of cerebellar granule cell precursors (GCPs) and its aberrant activation is a leading cause of Medulloblastoma, the most frequent pediatric brain tumor. We show here that the energy sensor AMPK inhibits Hh signaling by phosphorylating a single residue of human Gli1 that is not conserved in other species. Studies with selective agonists and genetic delet...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 2017