Deciphering the transcriptional alterations in high grade serous ovarian cancer upon catalytic inactivation of protein kinase D
To study the transcription alterations in high grade serous ovarian cancer upon catalytic inactivation of protein kinase D (PKD). PKD was catalytically inactivated in HGSOC cells OVCAR8 and SKOV3 by two highly selective, small molecule inhibitors CRT0066101, kb-NB142-70 and RNASeq analysis was performed to identify genes being differentially expressed upon this treatment. Gene Ontology and pathway analysis of the significantly differentially expressed transcripts were performed to identify the enriched biological process, molecular functions, and pathways. Comparative analysis identified 264 differentially expressed genes (131 and 133 genes up and downregulated, respectively) common among two PKD-inactivated HGSOC cell lines. Gene ontology (GO) analysis showed significantly enriched and functionally relevant physiological/biological processes including cell division, regulation of cell cycle and protein transport and chromatin organization. Molecular functions enriched in both cell lines after PKD inactivation were protein binding, ATP binding, protein kinase binding, transcription corepressor activity, chromatin binding, mRNA binding, ubiquitin protein ligase binding, microtubule binding and transcription factor binding. Among many, pathway analysis identified genes regulating cell proliferation, cell cycle and extracellular matrix remodelling - three paramount cellular processes that are dysregulated in HGSOC cells treated with PKD inhibitors. Collectively, our results showed that PKD and its downstream targets positively drive several tumorigenesis-associated cellular/physiological functions and could be therapeutically targeted against a lethal pathology like HOSOC.