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View article: Opposite effects of spermidine and GC7 in cell culture are dictated by distinct molecular targets
Opposite effects of spermidine and GC7 in cell culture are dictated by distinct molecular targets Open
Spermidine (SPD) and related polyamines are small polycationic molecules typically elevated in cancer cells, where their depletion suppresses tumor growth both in vitro and in vivo. Paradoxically, SPD has also been proposed as a dietary su…
View article: Colorectal cancer chemoprevention: Exploring the path from molecular mechanisms to available drugs
Colorectal cancer chemoprevention: Exploring the path from molecular mechanisms to available drugs Open
Colorectal cancer (CRC) remains a significant global health challenge despite advances in screening and diagnostic modalities that have contributed to reduced incidence and mortality. A substantial proportion of cases, however, continue to…
View article: MDB-29. SALL4 IS A CRL3REN/KCTD11 SUBSTRATE THAT DRIVES SONIC HEDGEHOG-DEPENDENT MEDULLOBLASTOMA
MDB-29. SALL4 IS A CRL3REN/KCTD11 SUBSTRATE THAT DRIVES SONIC HEDGEHOG-DEPENDENT MEDULLOBLASTOMA Open
BACKGROUND Medulloblastoma (MB) is the most common malignant pediatric brain tumor arising from alterations in cerebellum development. The Sonic Hedgehog variant (SHH MB) is the best genetically characterized, however the molecular mechani…
View article: Modeling Myotonic Dystrophy Type 2 Using Drosophila melanogaster
Modeling Myotonic Dystrophy Type 2 Using Drosophila melanogaster Open
Myotonic dystrophy 2 (DM2) is a genetic multi-systemic disease primarily affecting skeletal muscle. It is caused by CCTGn expansion in intron 1 of the CNBP gene, which encodes a zinc finger protein. DM2 disease has been successfully modele…
View article: Induction of Ferroptosis in Glioblastoma and Ovarian Cancers by a New Pyrrole Tubulin Assembly Inhibitor
Induction of Ferroptosis in Glioblastoma and Ovarian Cancers by a New Pyrrole Tubulin Assembly Inhibitor Open
We synthesized new aroyl diheterocyclic pyrrole (ARDHEP) 15 that exhibited the hallmarks of ferroptosis. Compound 15 strongly inhibited U-87 MG, OVCAR-3, and MCF-7 cancer cells, induced an increase of cleaved PARP, but was not toxic for no…
View article: A gene dosage‐dependent effect unveils NBS1 as both a haploinsufficient tumour suppressor and an essential gene for SHH‐medulloblastoma
A gene dosage‐dependent effect unveils NBS1 as both a haploinsufficient tumour suppressor and an essential gene for SHH‐medulloblastoma Open
Aims Inherited or somatic mutations in the MRE11 , RAD50 and NBN genes increase the incidence of tumours, including medulloblastoma (MB). On the other hand, MRE11, RAD50 and NBS1 protein components of the MRN complex are often overexpresse…
View article: The Mechanism of Action of Biguanides: New Answers to a Complex Question
The Mechanism of Action of Biguanides: New Answers to a Complex Question Open
Biguanides are a family of antidiabetic drugs with documented anticancer properties in preclinical and clinical settings. Despite intensive investigation, how they exert their therapeutic effects is still debated. Many studies support the …
View article: Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function
Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function Open
Microsatellite expansions of CCTG repeats in the cellular nucleic acid-binding protein ( CNBP ) gene leads to accumulation of toxic RNA and have been associated with myotonic dystrophy type 2 (DM2). However, it is still unclear whether the…
View article: Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function
Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function Open
Microsatellite expansions of CCTG repeats in the CNBP gene leads to accumulation of toxic RNA and have been associated to DM2. However, it is still unclear whether the dystrophic phenotype is also linked to CNBP decrease, a conserved CCHC-…
View article: Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation
Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation Open
Eukaryotic Translation Initiation Factor 5A (EIF5A) is a translation factor regulated by hypusination, a unique posttranslational modification catalyzed by deoxyhypusine synthetase (DHPS) and deoxyhypusine hydroxylase (DOHH) starting from …
View article: Clinical Multigene Panel Sequencing Identifies Distinct Mutational Association Patterns in Metastatic Colorectal Cancer
Clinical Multigene Panel Sequencing Identifies Distinct Mutational Association Patterns in Metastatic Colorectal Cancer Open
Extensive molecular characterization of human colorectal cancer (CRC) via Next Generation Sequencing (NGS) indicated that genetic or epigenetic dysregulation of a relevant, but limited, number of molecular pathways typically occurs in this…
View article: Phenformin Inhibits Hedgehog-Dependent Tumor Growth through a Complex I-Independent Redox/Corepressor Module
Phenformin Inhibits Hedgehog-Dependent Tumor Growth through a Complex I-Independent Redox/Corepressor Module Open
The antidiabetic drug phenformin displays potent anticancer activity in different tumors, but its mechanism of action remains elusive. Using Shh medulloblastoma as model, we show here that at clinically relevant concentrations, phenformin …
View article: Polyamine Metabolism as a Therapeutic Target in Hedgehog-Driven Basal Cell Carcinoma and Medulloblastoma
Polyamine Metabolism as a Therapeutic Target in Hedgehog-Driven Basal Cell Carcinoma and Medulloblastoma Open
Hedgehog (Hh) signaling is a critical developmental regulator and its aberrant activation, due to somatic or germline mutations of genes encoding pathway components, causes Basal Cell Carcinoma (BCC) and medulloblastoma (MB). A growing eff…
View article: Mitogen-activated kinase kinase kinase 1 inhibits hedgehog signaling and medulloblastoma growth through GLI1 phosphorylation
Mitogen-activated kinase kinase kinase 1 inhibits hedgehog signaling and medulloblastoma growth through GLI1 phosphorylation Open
The aberrant activation of hedgehog (HH) signaling is a leading cause of the development of medulloblastoma, a pediatric tumor of the cerebellum. The FDA‑approved HH inhibitor, Vismodegib, which targets the transmembrane transducer SMO, ha…
View article: Targeting class <scp>I</scp> histone deacetylases by the novel small molecule inhibitor 4<scp>SC</scp>‐202 blocks oncogenic hedgehog‐<scp>GLI</scp> signaling and overcomes smoothened inhibitor resistance
Targeting class <span>I</span> histone deacetylases by the novel small molecule inhibitor 4<span>SC</span>‐202 blocks oncogenic hedgehog‐<span>GLI</span> signaling and overcomes smoothened inhibitor resistance Open
Aberrant activation of Hedgehog (HH)/GLI signaling is causally involved in numerous human malignancies, including basal cell carcinoma (BCC) and medulloblastoma. HH pathway antagonists targeting smoothened (SMO), an essential effector of c…
View article: Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma
Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma Open
SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the t…
View article: The energy sensor AMPK regulates Hedgehog signaling in human cells through a unique Gli1 metabolic checkpoint
The energy sensor AMPK regulates Hedgehog signaling in human cells through a unique Gli1 metabolic checkpoint Open
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 inh…