Inhibiting ULK1 kinase decreases autophagy and cell viability in high-grade serous ovarian cancer spheroids.
Bipradeb Singha, Jeremi Laski, Yudith Ramos Valdés, Elaine Liu, Gabriel E. DiMattia, Trevor G. Shepherd
Abstract
mRNA expression is negatively correlated with patient survival among stage III and stage IV serous ovarian cancer patients. As we observed using established HGSOC cell lines, cultured spheroids using our new, patient-derived HGSOC cells were also sensitive to ULK1 inhibition and demonstrated reduced cell viability to MRT68921 treatment. These results demonstrate the importance of ULK1 for autophagy induction in HGSOC spheroids and therefore justifies further evaluation of MRT68921, and other novel ULK1 inhibitors, as potential therapeutics against metastatic HGSOC.
Topics & Concepts
AutophagyCancer researchULK1Ovarian cancerGene knockdownSpheroidViability assayChemistryCancer cellBiologyKinaseCell biologyProtein kinase ACellCancerMedicineCell cultureInternal medicineApoptosisAMPKBiochemistryGeneticsAutophagy in Disease and TherapyEndoplasmic Reticulum Stress and DiseaseEpigenetics and DNA Methylation