The metabolic demands of cancer cells are coupled to their size and protein synthesis rates

作者: Sonia C Dolfi , Leo Li-Ying Chan , Jean Qiu , Philip M Tedeschi , Joseph R Bertino

DOI: 10.1186/2049-3002-1-20

关键词: BioinformaticsGeneCancer cellCell cultureCell biologyCellCell growthBiologyMesenchymal stem cellGene expressionVimentin

摘要: Although cells require nutrients to proliferate, most nutrient exchange rates of the NCI60 panel cancer cell lines correlate poorly with their proliferation rate. Here, we provide evidence indicating that this inconsistency is rooted in variability size. We integrate previously reported data characterizing genome copy number variations, gene expression, protein expression and fluxes our own measurements size content lines. show content, DNA synthesis per are proportional volume, larger proliferate slower than smaller cells. estimate metabolic these magnitudes rate and, after correcting for At level observe genes expressed at higher levels enriched involved cycle, while large mesenchymal The latter finding further corroborated by induction those same following treatment TGFβ, high vimentin but low E-cadherin also find aromatase inhibitors, statins mTOR inhibitors preferentially inhibit vitro growth cell. display various activities, type activity they possess correlates volume content. In addition proliferation, and/or biomarkers may predict response drugs targeting metabolism.

参考文章(55)
Kevin R. Short, Jonas Nygren, Rocco Barazzoni, James Levine, K. Sreekumaran Nair, T3 increases mitochondrial ATP production in oxidative muscle despite increased expression of UCP2 and -3 American Journal of Physiology-endocrinology and Metabolism. ,vol. 280, ,(2001) , 10.1152/AJPENDO.2001.280.5.E761
Emmanuel Barillot, Valentina Boeva, Elodie Manié, Tatiana Popova, Marc-Henri Stern, Yves Rozenholc, Analysis of Somatic Alterations in Cancer Genome: From SNP Arrays to Next Generation Sequencing ,(2013)
Leo L Chan, Xuemei Zhong, Jean Qiu, Peter Y Li, Bo Lin, None, Cellometer vision as an alternative to flow cytometry for cell cycle analysis, mitochondrial potential, and immunophenotyping. Cytometry Part A. ,vol. 79, pp. 507- 517 ,(2011) , 10.1002/CYTO.A.21071
Thomas R Kiehl, Duan Shen, Sarwat F Khattak, Zheng Jian Li, Susan T Sharfstein, None, Observations of cell size dynamics under osmotic stress Cytometry Part A. ,vol. 79, pp. 560- 569 ,(2011) , 10.1002/CYTO.A.21076
R. Wibom, E. Hultman, M. Johansson, K. Matherei, D. Constantin-Teodosiu, P. G. Schantz, Adaptation of mitochondrial ATP-production in human skeletal muscle to endurance training and detraining Journal of Applied Physiology. ,vol. 73, pp. 2004- 2010 ,(1992) , 10.1152/JAPPL.1992.73.5.2004
Ulla Glas, Gunter F. Bahr, Quantitative study of mitochondria in rat liver. Dry mass, wet mass, volume, and concentration of solids. Journal of Cell Biology. ,vol. 29, pp. 507- 523 ,(1966) , 10.1083/JCB.29.3.507
Katrin Düvel, Jessica L. Yecies, Suchithra Menon, Pichai Raman, Alex I. Lipovsky, Amanda L. Souza, Ellen Triantafellow, Qicheng Ma, Regina Gorski, Stephen Cleaver, Matthew G. Vander Heiden, Jeffrey P. MacKeigan, Peter M. Finan, Clary B. Clish, Leon O. Murphy, Brendan D. Manning, Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1 Molecular Cell. ,vol. 39, pp. 171- 183 ,(2010) , 10.1016/J.MOLCEL.2010.06.022
X‐Y Hou, Simon Green, Christopher D Askew, Glenn Barker, Anita Green, PJ Walker, None, Skeletal muscle mitochondrial ATP production rate and walking performance in peripheral arterial disease Clinical Physiology and Functional Imaging. ,vol. 22, pp. 226- 232 ,(2002) , 10.1046/J.1475-097X.2002.00423.X