Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Published Online November 20, 2008
Science DOI: 10.1126/science.1160165

Research Articles

Submitted on May 7, 2008
Accepted on October 31, 2008

Dynamic Proteomics of Individual Cancer Cells in Response to a Drug

A. A. Cohen 1{dagger}*, N. Geva-Zatorsky 1{dagger}, E. Eden 1{dagger}, 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. Alon 1

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

* To whom correspondence should be addressed.
A. A. Cohen , E-mail: ariel.cohen{at}weizmann.ac.il

{dagger}These authors contributed equally to this work.

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 individual 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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Non-genetic heterogeneity of cells in development: more than just noise.
S. Huang (2009)
Development 136, 3853-3862
   Abstract »    Full Text »    PDF »
Determinism and divergence of apoptosis susceptibility in mammalian cells.
P. D. Bhola and S. M. Simon (2009)
J. Cell Sci. 122, 4296-4302
   Abstract »    Full Text »    PDF »
Dynamic Proteomics: a database for dynamics and localizations of endogenous fluorescently-tagged proteins in living human cells.
M. Frenkel-Morgenstern, A. A. Cohen, N. Geva-Zatorsky, E. Eden, J. Prilusky, I. Issaeva, A. Sigal, C. Cohen-Saidon, Y. Liron, L. Cohen, et al. (2009)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.
S. Ocak, M. L. Sos, R. K. Thomas, and P. P. Massion (2009)
Eur. Respir. J. 34, 489-506
   Abstract »    Full Text »    PDF »
Toxicity Testing in the 21st Century: A View from the Pharmaceutical Industry.
J. S. MacDonald and R. T. Robertson (2009)
Toxicol. Sci. 110, 40-46
   Full Text »    PDF »
Quantitative Assessment of the Complex Dynamics of G1, S, and G2-M Checkpoint Activities.
P. Ubezio, M. Lupi, D. Branduardi, P. Cappella, E. Cavallini, V. Colombo, G. Matera, C. Natoli, D. Tomasoni, and M. D'Incalci (2009)
Cancer Res. 69, 5234-5240
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)