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Originally published in Science Express on 20 November 2008
Science 5 December 2008:
Vol. 322. no. 5907, pp. 1511 - 1516
DOI: 10.1126/science.1160165
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Research Articles

Dynamic Proteomics of Individual Cancer Cells in Response to a Drug

A. A. Cohen,1*{dagger} N. Geva-Zatorsky,1* E. Eden,1* M. Frenkel-Morgenstern,1 I. Issaeva,1 A. Sigal,2 R. Milo,3 C. Cohen-Saidon,1 Y. Liron,1 Z. Kam,1 L. Cohen,1 T. Danon,1 N. Perzov,1 U. Alon1

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.

1 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
2 Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
3 Department of Plant Sciences, Weizmann Institute of Science, Rehovot 76100, Israel.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ariel.cohen{at}weizmann.ac.il

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