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  • Open Access

Cell proliferation and tissue remodeling are major determinants of cancer metabolism and the response to drugs targeting metabolism

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Cancer & Metabolism20142 (Suppl 1) :P80

  • Published:


  • Cancer Cell
  • Cell Proliferation
  • Cancer Cell Line
  • Human Cancer
  • Gene Expression Profile


Alterations in cell proliferation and tissue remodeling are major hallmarks of cancer. Given that these two physiological processes require a significant investment of metabolic resources, we hypothesize that the metabolism of cancer cells is, in a first approximation, determined by the magnitude of cell proliferation and tissue remodeling.

Materials and methods

To address this question in further detail we have analyzed in vitro data characterizing cancer cell lines and gene expression profiles of human cancers.


We show that the metabolism of cancer cells is strongly correlated with cell proliferation and tissue remodeling. Based on in vitro data, cancer cell lines align from an extreme of highly proliferating cells of relatively small size to another extreme of slowly proliferating cells with large size and mesenchymal properties [1]. Similarly, in human cancers we detect a strong negative correlation between gene signatures associated with cell proliferation and tissue remodeling [2]. The stratification of human cancers based on the cell-proliferation/ tissue-remodeling signatures results in divergence in the survival plots as significant as those obtained using current site-specific classifications. Furthermore, in vitro data suggest that these different subtypes have a differential sensitivity to diverse drug classes targeting metabolism [1].


We conclude that human cancers can be subject to a universal cell-proliferation/tissue-remodeling classification independent of their site of origin that can guide personalized treatment targeting cancer metabolism.

Authors’ Affiliations

Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA


  1. Dolfi SC, Chan LL, Qiu J, Tedeschi PM, Bertino JR, Hirshfield KM, Oltvai ZN, Vazquez A: The metabolic demands of cancer cells are coupled to their size and protein synthesis rates. Cancer Metab. 2013, 1: 20-10.1186/2049-3002-1-20.PubMed CentralView ArticlePubMedGoogle Scholar
  2. Markert EK, Levine AJ, Vazquez A: Proliferation and tissue remodeling in cancer: the hallmarks revisited. Cell Death Dis. 2012, 3: e397-10.1038/cddis.2012.140.PubMed CentralView ArticlePubMedGoogle Scholar


© Markert et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.