theJONESlab

Cancer metabolism & immunology

Goodman Cancer Research Centre | Department of Physiology | McGill University

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Cancer metabolism to drive growth

The ability to engage in increased glycolytic metabolism might be advantageous for growth of cancer cells beyond the ability to rapidly generate energy and suppress apoptosis. This raises a crucial question – what are the metabolic pathways important for growth in proliferating cancer cells? My research group is focused on investigating how signal transduction pathways can redirect metabolic pathways for biosynthesis to enable cell proliferation. Our group focuses on defining the molecular regulators of this process, with particular attention on how the LKB1/AMPK nutrient energy sensing pathway regulates this process. We have recently discovered novel connections between the microRNA cluster miR-17~92 and control of cellular metabolism through regulation of LKB1.

Surviving lean times

Increased metabolic potential, while supportive of unchecked growth, poses a distinct metabolic challenge for tumour cells. Once a growing tumour outstrips its nutrient supply, it must enact strategies to maintain cellular bioenergetics. Thus, how tumours engage strategies of metabolic adaptation to survive stress may contribute to cancer progression and outcome (i.e. metastasis). Our research in this area has focused on the metabolic regulator AMPK and its role in promoting adaptation to metabolic stress. More recent work has identified pathways that tumour cells use to proliferate when glucose is limiting, which includes co-opting parts of gluconeogenesis to use TCA cycle intermediates for biosynthesis. Our future efforts are focused on identifying novel pathways that mediate cellular adaptation to stress.