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Sci. Signal., 21 July 2009
Vol. 2, Issue 80, p. ra35
[DOI: 10.1126/scisignal.2000369]


Editor's Summary

Preventing Metastatic Spread
The tumor suppressor p53 promotes anoikis, the apoptotic death of cells that lose adhesion and become detached from their appropriate location, thereby suppressing cancer metastasis. Here, Cheng et al. show that the serine-threonine kinase SIK1 (salt-inducible kinase 1) regulates p53-dependent anoikis. Loss of SIK1 facilitated the anchorage-independent growth of cultured cells and promoted the development of micrometastases in the absence of primary tumors in immunodeficient mice. Moreover, decreased SIK1 expression correlated with appearance of distal metastases in human breast cancer. The authors propose that SIK1, by promoting anoikis, prevents the dissemination of precancerous cells and thereby plays a critical role in inhibiting metastasis.

Citation: H. Cheng, P. Liu, Z. C. Wang, L. Zou, S. Santiago, V. Garbitt, O. V. Gjoerup, J. D. Iglehart, A. Miron, A. L. Richardson, W. C. Hahn, J. J. Zhao, SIK1 Couples LKB1 to p53-Dependent Anoikis and Suppresses Metastasis. Sci. Signal. 2, ra35 (2009).

Read the Full Text

Contribution of p53 to Metastasis.
E. Powell, D. Piwnica-Worms, and H. Piwnica-Worms (2014)
Cancer Discovery 4, 405-414
   Abstract »    Full Text »    PDF »
AMPK: A Contextual Oncogene or Tumor Suppressor?.
J. Liang and G. B. Mills (2013)
Cancer Res. 73, 2929-2935
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Supervillin-mediated Suppression of p53 Protein Enhances Cell Survival.
Z. Fang and E. J. Luna (2013)
J. Biol. Chem. 288, 7918-7929
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Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis.
S. M. Frisch, M. Schaller, and B. Cieply (2013)
J. Cell Sci. 126, 21-29
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Lkb1 regulates organogenesis and early oncogenesis along AMPK-dependent and -independent pathways.
B. Lo, G. Strasser, M. Sagolla, C. D. Austin, M. Junttila, and I. Mellman (2012)
J. Cell Biol. 199, 1117-1130
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Salt-inducible kinase 1 regulates E-cadherin expression and intercellular junction stability.
K. Eneling, L. Brion, V. Pinto, M. J. Pinho, J. I. Sznajder, N. Mochizuki, K. Emoto, P. Soares-da-Silva, and A. M. Bertorello (2012)
FASEB J 26, 3230-3239
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A Pathway for the Control of Anoikis Sensitivity by E-Cadherin and Epithelial-to-Mesenchymal Transition.
S. Kumar, S. H. Park, B. Cieply, J. Schupp, E. Killiam, F. Zhang, D. L. Rimm, and S. M. Frisch (2011)
Mol. Cell. Biol. 31, 4036-4051
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Making sense of cancer genomic data.
L. Chin, W. C. Hahn, G. Getz, and M. Meyerson (2011)
Genes & Dev. 25, 534-555
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Alternative cell death mechanisms in development and beyond.
J. Yuan and G. Kroemer (2010)
Genes & Dev. 24, 2592-2602
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Understanding Micrometastatic Disease and Anoikis Resistance in Ewing Family of Tumors and Osteosarcoma.
S. J. Strauss, T. Ng, A. Mendoza-Naranjo, J. Whelan, and P. H. B. Sorensen (2010)
Oncologist 15, 627-635
   Abstract »    Full Text »    PDF »
Tumor Suppression by LKB1: SIK-ness Prevents Metastasis.
R. J. Shaw (2009)
Science Signaling 2, pe55
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