title: Ivermectin induces PAK1-mediated cytostatic autophagy in breast cancer.
abstract: Ivermectin is a broad-spectrum antiparasitic drug that has recently been demonstrated to exhibit potent anticancer activity against colon cancer, ovarian cancer, melanoma and leukemia. However, the molecular mechanism underlying this anticancer effect remains poorly understood. We recently found that ivermectin markedly inhibits the growth of breast cancer cells by stimulating cytostatic macroautophagy/autophagy in vitro and in vivo. Ivermectin inhibits the AKT-MTOR signaling pathway by promoting ubiquitination-mediated degradation of PAK1 (p21 [RAC1] activated kinase 1), leading to increased autophagic flux. Together, our work unravels the molecular mechanism underpinning ivermectin-induced cytostatic autophagy in breast cancer, and characterizes ivermectin as a potential therapeutic option for breast cancer treatment.
authors.affiliation: a State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , China.
authors.forename: Kui
authors.initials: K
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , China.|b Key Laboratory of Tropical Diseases and Translational Medicine of Ministry of Education and Department of Neurology , Affiliated Hospital of Hainan Medical College , Haikou , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: a State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , China.
authors.forename: Qianhui
authors.initials: Q
authors.lastname: Dou
authors.affiliation: c Department of Gastrointestinal Surgery , West China Hospital, Sichuan University , Chengdu , China.
authors.forename: Haining
authors.initials: H
authors.lastname: Chen
authors.affiliation: b Key Laboratory of Tropical Diseases and Translational Medicine of Ministry of Education and Department of Neurology , Affiliated Hospital of Hainan Medical College , Haikou , China.
authors.forename: Qifu
authors.initials: Q
authors.lastname: Li
authors.affiliation: d Department of Biochemistry and Molecular Biology , Monash University, Clayton , Victoria , Australia.
authors.forename: Edouard C
authors.initials: EC
authors.lastname: Nice
authors.affiliation: a State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy , Chengdu , China.|b Key Laboratory of Tropical Diseases and Translational Medicine of Ministry of Education and Department of Neurology , Affiliated Hospital of Hainan Medical College , Haikou , China.
authors.forename: Canhua
authors.initials: C
authors.lastname: Huang
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D054697:Cytostatic Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007559:Ivermectin / Q000494:pharmacology*; D008954:Models, Biological; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D054697:Cytostatic Agents; D007559:Ivermectin; D051057:Proto-Oncogene Proteins c-akt; D054462:p21-Activated Kinases
keywords: AKT; PAK1; breast cancer; cytostatic autophagy; ivermectin