Pharmacological Inactivation of Skp2 SCF Ubiquitin Ligase Restricts Cancer Stem Cell Traits and Cancer Progression

• Published in: Cell Vol. 154; no. 3; pp. 556 - 568
• Main Authors: Chan, Chia-Hsin, Morrow, John Kenneth, Li, Chien-Feng, Gao, Yuan, Jin, Guoxiang, Moten, Asad, Stagg, Loren J., Ladbury, John E., Cai, Zhen, Xu, Dazhi, Logothetis, Christopher J., Hung, Mien-Chie, Zhang, Shuxing, Lin, Hui-Kuan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2013
• Subjects: animal models; Animals; antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; cell cycle; cell senescence; cell viability; cells; Disease Models, Animal; Drug Discovery; Drug Screening Assays, Antitumor; drug therapy; Genes, p53; glycolysis; Glycolysis - drug effects; Humans; ligases; metastasis; Mice; Mice, Nude; Models, Molecular; Multienzyme Complexes - antagonists & inhibitors; Multienzyme Complexes - chemistry; Multienzyme Complexes - metabolism; Neoplasm Transplantation; neoplasms; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - genetics; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; population; S-Phase Kinase-Associated Proteins - antagonists & inhibitors; S-Phase Kinase-Associated Proteins - chemistry; S-Phase Kinase-Associated Proteins - metabolism; screening; senescence; Small Molecule Libraries; stem cells; Structure-Activity Relationship; Transplantation, Heterologous; ubiquitin-protein ligase; Ubiquitin-Protein Ligases - antagonists & inhibitors; Ubiquitin-Protein Ligases - chemistry; Ubiquitin-Protein Ligases - metabolism

Skp2 E3 ligase is overexpressed in numerous human cancers and plays a critical role in cell-cycle progression, senescence, metabolism, cancer progression, and metastasis. In the present study, we identified a specific Skp2 inhibitor using high-throughput in silico screening of large and diverse chem...