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Differential Effector Engagement by Oncogenic KRAS

  1. Author:
    Yuan, Tina L
    Amzallag, Arnaud
    Bagni, Rachel
    Yi, Ming
    Afghani, Shervin
    Burgan, William
    Fer, Nicole
    Strathern, Leslie
    Powell, Katie
    Smith, Brian
    Waters, Andrew M
    Drubin, David
    Thomson, Ty
    Liao, Rosy
    Greninger, Patricia
    Stein, Giovanna T
    Murchie, Ellen
    Cortez, Eliane
    Egan, Regina K
    Procter, Lauren
    Bess, Matthew
    Cheng, Oscar
    Lee, Chih-Shia
    Lee, Liam Changwoo
    Fellmann, Christof
    Stephens, Bob
    Luo, Ji
    Lowe, Scott W
    Benes, Cyril H
    McCormick, Frank

  2. Author Address

    Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 3rd Street, San Francisco, CA 94158, USA., Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA., Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., P.O. Box B, Frederick, MD 21702, USA., Selventa, One Alewife Center, Suite 330, Cambridge, MA 02140, USA., Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA., Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Department of Cancer Biology & Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute, New York, NY 10065, USA., Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Electronic address: cbenes@mgh.harvard.edu., Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 3rd Street, San Francisco, CA 94158, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., P.O. Box B, Frederick, MD 21702, USA. Electronic address: frank.mccormick@ucsf.edu.,
    1. Year: 2018
    2. Date: Feb 13
  2. Journal: Cell Reports
    1. 22
    2. 7
    3. Pages: 1889-1902
  4. Type of Article: Article
  5. ISSN: 2211-1247
  1. Abstract:

    KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase, and RalGDS families, but many additional direct and indirect effectors have been reported. We have assessed how these effectors contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in which we knocked down 41 KRAS effectors nodes in 92 cell lines. We show that every cell line has a unique combination of effector dependencies, but in spite of this heterogeneity, we were able to identify two major subtypes of KRAS mutant cancers of the lung, pancreas, and large intestine, which reflect different KRAS effector engagement and opportunities for therapeutic intervention. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2018.01.051
  3. PMID: 29444439
  4. View record in Web of Science®
  5. WOS: 000424981600022
  6. PII : S2211-1247(18)30083-4

Library Notes

  1. Fiscal Year: FY2017-2018
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