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Cancer Metabolism

cancer metabolism

Tumor cells develop a variety of metabolic strategies to maintain exacerbated growth and survival. The specific identification of the genetic and epigenetic factors causing this metabolic phenotype is essential to exploit metabolic vulnerabilities for cancer therapy.

At the center of these vulnerabilities are the mitochondrial-based metabolic pathways that required for maintenance of cell survival and progression of cell division. Our laboratory is interested in the identification of the genetic factors as well as metabolic components that are necessary for tumor progression. We use a broad experimental approach based on the use of publically available data sets, screening of human tumor cell lines, and validation in mouse models.

We have recently applied this experimental design to identify a subset of human melanoma tumors that aberrantly overexpress the transcriptional co-activator PGC-1α and exhibit increased mitochondrial energy metabolism and ROS detoxification. These metabolic capacities allow this subset of tumors to display increased rates of survival under oxidative stress.

Selected publications

A PGC1α-mediated transcriptional axis suppresses melanoma metastasis.
Luo C, Lim JH, Lee Y, Granter SR, Thomas A, Vazquez F, Widlund HR, Puigserver P.

Nature. 537(7620):422-426, 2016

Targeting mitochondrial oxidative metabolism in melanomas causes metabolic compensation through glucose and glutamine utilization.
Lim JH, Luo C, Vazquez F, Puigserver P.

Cancer Res. 74(13):3535-45, 2014

PGC-1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress
F. Vazquez, J.H. Lim, H. Chim, K. Bhalla, G. Girnun, C.B. Clish, S.R. Granter, H.R. Windlund, B.M. Spiegelman and P. Puigserver
Cancer Cell23(3):287-301, 2013

Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachments
Z.T. Schafer, A.R. Grassian, L. Song, Z. Jiang, Z. Gerhart-Hines, H.Y. Irie, S. Gao, P. Puigserver and J. S. Brugge
Nature. 461(7260):109-13, 2009

Full list of publications