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Dynamic Proteomics of Individual Cancer Cells in Response to a Drug

Cohen, A. A. and Geva-Zatorsky, N. and Eden, E. and Frenkel-Morgenstern, M. and Issaeva, I. and Sigal, A. and Milo, R. and Cohen-Saidon, C. and Liron, Y. and Kam, Z. and Cohen, L. and Danon, T. and Perzov, N. and Alon, U. (2008) Dynamic Proteomics of Individual Cancer Cells in Response to a Drug. Science, 322 (5907). pp. 1511-1516. ISSN 0036-8075. http://resolver.caltech.edu/CaltechAUTHORS:COHsci08

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Abstract

Why do seemingly identical cells respond differently to a drug? To address this, we studied the dynamics and variability of the protein response of human cancer cells to a chemotherapy drug, camptothecin. We present a dynamic-proteomics approach that measures the levels and locations of nearly 1000 different endogenously tagged proteins in individual living cells at high temporal resolution. All cells show rapid translocation of proteins specific to the drug mechanism, including the drug target (topoisomerase-1), and slower, wide-ranging temporal waves of protein degradation and accumulation. However, the cells differ in the behavior of a subset of proteins. We identify proteins whose dynamics differ widely between cells, in a way that corresponds to the outcomes—cell death or survival. This opens the way to understanding molecular responses to drugs in individual cells.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.116016DOIUNSPECIFIED
http://www.sciencemag.org/cgi/content/abstract/322/5907/1511PublisherUNSPECIFIED
http://www.sciencemag.org/cgi/content/full/sci;1160165/DC1PublisherUNSPECIFIED
Additional Information:© 2008 American Association for the Advancement of Science. Received for publication 7 May 2008. Accepted for publication 31 October 2008. Originally published in Science Express on 20 November 2008. We thank the Kahn Family Foundation and the Israel Science Foundation for support. We thank E. Zalckvar, J. Bar, I. Glinert, T. Shlapok, and members of the Alon laboratory for discussions. The work of M.F.-M. and E.E. is supported by the Yeshaya Horowitz Association through the Center for Complexity Science. upporting Online Material: http://www.sciencemag.org/cgi/content/full/1160165/DC1 Materials and Methods; SOM Text; Figs. S1 to S20; Tables S1 to S4; References; Movies S1 to S4
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Funding AgencyGrant Number
Kahn Family FoundationUNSPECIFIED
Israel Science FoundationUNSPECIFIED
Yeshaya Horowitz AssociationUNSPECIFIED
Issue or Number:5907
Record Number:CaltechAUTHORS:COHsci08
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:COHsci08
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:12527
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:16 Dec 2008 01:09
Last Modified:26 Dec 2012 10:34

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