Akt1 depletion in murine ovarian granulosa cells reveals known and novel molecular and cellular processes dependent on this kinase

ABSTRACT: The PI3K/AKT signaling pathway is known to regulate a broad range of cellular processes and it is often altered in several types of cancers. Recently, somatic AKT1 mutations leading to a strong activation of this kinase have been reported in juvenile granulosa cell tumors. However, the molecular role of AKT1 in the ovary is still poorly understood. To get insights into its ovarian function, we depleted Akt1 in murine primary granulosa cells, a supporting cell lineage, and assessed the molecular consequences at both the transcript and protein levels. We were able to corroborate the involvement of AKT1 in metabolism, apoptosis, cell cycle or cytoskeleton regulation in granulosa cells. Consistently, we showed that established granulosa cells depleted for Akt1 exhibited increased velocity and altered directional persistent migration. This study also allowed us to uncover new direct and indirect targets of the kinase. Indeed, a series of proteins involved in intracellular transport and mitochondrial physiology were also significantly affected by Akt1 depletion. Using in silico analyses, we also propose a set of kinases and transcription factors that can mediate the action of AKT1 on the deregulated transcripts and proteins. Taken altogether, our results provide a resource of direct and indirect AKT1 targets in the ovary and may shed light on the molecular events driving tumorigenesis owing to its mutations in granulosa cells.

OTHER RELATED OMICS DATASETS IN: GSE130187

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Ovary, Granulosa Cell

SUBMITTER: Thibaut LEGER  

LAB HEAD: Reiner A. VEITIA

PROVIDER: PXD012548 | Pride | 2019-04-30

REPOSITORIES: Pride