11 research outputs found
AMPK activation protects against prostate cancer by inducing a catabolic cellular state
Emerging evidence indicates that metabolic dysregulation drives prostate cancer (PCa) progression and metastasis. AMP-activated protein kinase (AMPK) is a master regulator of metabolism, although its role in PCa remains unclear. Here, we show that genetic and pharmacological activation of AMPK provides a protective effect on PCa progression in vivo. We show that AMPK activation induces PGC1α expression, leading to catabolic metabolic reprogramming of PCa cells. This catabolic state is characterized by increased mitochondrial gene expression, increased fatty acid oxidation, decreased lipogenic potential, decreased cell proliferation, and decreased cell invasiveness. Together, these changes inhibit PCa disease progression. Additionally, we identify a gene network involved in cell cycle regulation that is inhibited by AMPK activation. Strikingly, we show a correlation between this gene network and PGC1α gene expression in human PCa. Taken together, our findings support the use of AMPK activators for clinical treatment of PCa to improve patient outcome
Systemic muscle wasting and coordinated tumour response drive tumourigenesis
Cancer cells demand excess nutrients to support their proliferation, but how tumours exploit extracellular amino acids during systemic metabolic perturbations remain incompletely understood. Here, we use a Drosophila model of high-sugar diet (HSD)-enhanced tumourigenesis to uncover a systemic host-tumour metabolic circuit that supports tumour growth. We demonstrate coordinate induction of systemic muscle wasting with tumour-autonomous Yorkie-mediated SLC36-family amino acid transporter expression as a proline-scavenging programme to drive tumourigenesis. We identify Indole-3-propionic acid as an optimal amino acid derivative to rationally target the proline-dependency of tumour growth. Insights from this whole-animal Drosophila model provide a powerful approach towards the identification and therapeutic exploitation of the amino acid vulnerabilities of tumourigenesis in the context of a perturbed systemic metabolic network
Event-based prospective memory in depression: The impact of cue focality
This study is the first to compare event-based prospective memory performance in individuals with depression and healthy controls. The degree to which self-initiated processing is required to perform the prospective memory task was varied. Twenty-eight individuals with depression and 32 healthy controls worked on a computerised prospective memory task. Prospective cues were either presented focally or non-focally to the ongoing activity. Collapsing data across both conditions, controls outperformed individuals with depression in the prospective memory task. Overall, participants showed a poorer prospective memory performance in the non-focal condition that required self-initiated processing to a higher degree than the focal condition. Importantly, as revealed by a group by task condition interaction, groups did not differ in the focal condition, whereas, controls outperformed individuals with depression in the non-focal condition. The results are in line with the multiprocess framework of event-based prospective remembering and the cognitive-initiative account of depression-related cognitive deficits