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New research uncovers diverse metabolic roles for PML tumor suppressor gene
Date:8/30/2012

red mouse models. In other words, when PML is highly expressed, cellular metabolism is enhanced and the mice were able to briskly burn fat and avoid gaining weight. Conversely, when PML was lost, the animals grew obese.

But, the team also made the paradoxical discovery that PML's enhanced cellular metabolism appeared to provide breast cancer cells with the energy needed to survive. These findings are further supported by data showing PML is highly expressed in a subset of breast cancers with poor prognosis, notes Carracedo. Instead of maintaining its function as a tumor suppressor and keeping breast cancer cells under control, PML is providing breast cancer with a survival advantage. These findings aligned with work by other labs that have found a relationship between high PML expression and breast cancers with poor prognosis.

In the second paper, in the September 2012 issue of Nature Medicine, Keisuke Ito, MD PhD, together with co-lead author Arkaitz Carracedo, looked at PML's role in regulating hematopoetic stem cells (HSCs), again through the FAO pathway, and defined for the first time the contribution of lipid metabolism to maintaining the function of HSCs.

HSCs replenish blood cells throughout the lifespan of an organism, and so they are critical to the aging process, explains Ito, also a former postdoctoral fellow in the Pandolfi laboratory and currently a member of the faculty at the Albert Einstein College of Medicine. The authors discovered that inhibition of fatty acid oxidation could represent an effective therapy for leukemia, as well as other forms of cancer but that it simultaneously posed a risk to the replenishment of HSCs. "Our results uncover a crucial metabolic requirement involving PPAR-delta signaling and FAO for preservation of the delicate equilibrium between HSC maintenance and function," the authors write. The findings have straightforward therapeutic implications for the improvement of both the efficacy o
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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