Abemaciclib induces atypical cell death in cancer cells characterized by formation of cytoplasmic vacuoles derived from lysosomes

• Published in: Cancer science Vol. 111; no. 6; pp. 2132 - 2145
• Main Authors: Hino, Hirotsugu, Iriyama, Noriyoshi, Kokuba, Hiroko, Kazama, Hiromi, Moriya, Shota, Takano, Naoharu, Hiramoto, Masaki, Aizawa, Shin, Miyazawa, Keisuke
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.06.2020; John Wiley and Sons Inc
• Subjects: abemaciclib; Acidification; Adenosine triphosphatase; Alzheimer's disease; Apoptosis; Autophagy; Breast cancer; Cancer therapies; CDK4/6 inhibitor; Cell cycle; Cell death; Cell growth; Concanamycin A; Cyclin D; Cyclin-dependent kinase 4; Cycloheximide; Cytotoxicity; Dextran; G1 phase; Genotype & phenotype; Kinases; Lung cancer; lysosome; Lysosomes; Morphology; Necroptosis; Non-small cell lung carcinoma; Organelles; Original; Phagocytosis; Phagosomes; Phenotypes; Phosphorylation; Proteins; Transcription factors; Transmission electron microscopy; Tumor cell lines; vacuole formation; Vacuoles; V‐ATPase; vacuole formation; V-ATPase; lysosome; abemaciclib; CDK4/6 inhibitor

In the cell cycle, the G1/S transition is controlled by the cyclin‐dependent kinase (CDK) 4/6‐cyclin D complex. Constitutive activation of CDK4/6 dysregulates G1/S transition, leading to oncogenic transformation. We found that 3 CDK4/6 inhibitors, abemaciclib, ribociclib, and palbociclib, exerted a...