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CDK8 is a colorectal cancer oncogene that regulates β-catenin activity

Author

Listed:
  • Ron Firestein

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Department of Pathology,
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Adam J. Bass

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Department of Medicine and,
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • So Young Kim

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Department of Medicine and,
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Ian F. Dunn

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Serena J. Silver

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Isil Guney

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Ellen Freed

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA)

  • Azra H. Ligon

    (Department of Pathology,)

  • Natalie Vena

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA)

  • Shuji Ogino

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Department of Pathology,)

  • Milan G. Chheda

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Pablo Tamayo

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Stephen Finn

    (Department of Pathology,)

  • Yashaswi Shrestha

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Jesse S. Boehm

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Supriya Jain

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA)

  • Emeric Bojarski

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA)

  • Craig Mermel

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Jordi Barretina

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Jennifer A. Chan

    (Department of Pathology,
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Jose Baselga

    (Hospital Vall d’Hebron, Passeig Vall d’Hebron, 119-129, 08035 Barcelona, Spain)

  • Josep Tabernero

    (Hospital Vall d’Hebron, Passeig Vall d’Hebron, 119-129, 08035 Barcelona, Spain)

  • David E. Root

    (Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Charles S. Fuchs

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA)

  • Massimo Loda

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Department of Pathology,)

  • Ramesh A. Shivdasani

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Department of Medicine and,)

  • Matthew Meyerson

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Department of Pathology,
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • William C. Hahn

    (Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Department of Medicine and,
    Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA
    Broad Institute of Harvard and M.I.T., 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

Abstract

CCK8 and WNT signalling linked in colorectal cancer The WNT/ β-catenin signalling pathway, which normally plays a pivotal part in development, is deregulated in almost all colorectal cancers. Retinoblastoma tumour suppressor protein (pRB) is a cell-cycle regulator that is mutated in many different types of cancer. Two papers in this issue show that signalling through the WNT pathway and that mediated by pRB are highly interconnected, and that a common denominator of their deregulation is colorectal cancer. Firestein et al. combined RNAi screening for genes required for colon cancer cell proliferation with genomic data from human colon cancer to identifty CDK8 as a novel human oncogene. CDK8, a general transcriptional regulator, functions in part by enhancing the activity of the Wnt signalling pathway. Morris et al. report that E2F1, a transcription factor that is a target of pRB, is a potent and specific inhibitor of β-catenin, and that its activity is negatively regulated by CDK8. They point out that the interaction between E2F1 and β-catenin explains the long-standing paradox that pRB, an important tumour suppressor in most other contexts, is preserved in colorectal carcinomas. In an accompanying News & Views, René Bernards considers how the crosstalk between E2F and β-catenin signalling can lead to colorectal cancer.

Suggested Citation

  • Ron Firestein & Adam J. Bass & So Young Kim & Ian F. Dunn & Serena J. Silver & Isil Guney & Ellen Freed & Azra H. Ligon & Natalie Vena & Shuji Ogino & Milan G. Chheda & Pablo Tamayo & Stephen Finn & Y, 2008. "CDK8 is a colorectal cancer oncogene that regulates β-catenin activity," Nature, Nature, vol. 455(7212), pages 547-551, September.
    • Handle: RePEc:nat:nature:v:455:y:2008:i:7212:d:10.1038_nature07179
    DOI: 10.1038/nature07179
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    Citations

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    Cited by:

    1. Biaobin Jiang & Quanhua Mu & Fufang Qiu & Xuefeng Li & Weiqi Xu & Jun Yu & Weilun Fu & Yong Cao & Jiguang Wang, 2021. "Machine learning of genomic features in organotropic metastases stratifies progression risk of primary tumors," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Sandor Spisak & David Chen & Pornlada Likasitwatanakul & Paul Doan & Zhixin Li & Pratyusha Bala & Laura Vizkeleti & Viktoria Tisza & Pushpamali Silva & Marios Giannakis & Brian Wolpin & Jun Qi & Nilay, 2024. "Identifying regulators of aberrant stem cell and differentiation activity in colorectal cancer using a dual endogenous reporter system," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Jenny Zhe Liao & Hyung-lok Chung & Claire Shih & Kenneth Kin Lam Wong & Debdeep Dutta & Zelha Nil & Catherine Grace Burns & Oguz Kanca & Ye-Jin Park & Zhongyuan Zuo & Paul C. Marcogliese & Katherine S, 2024. "Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation and can phenotypically suppress pink1 deficiency in Drosophila," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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