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Sci. Signal., 21 July 2009
Vol. 2, Issue 80, p. ra35
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).