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p27Kip1 as a Biomarker and Target for Treatment of Cancer

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Book cover Checkpoint Controls and Targets in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

p27Kip1 (p27) is a critical cyclin dependent kinase inhibitor that negatively regulates cell cycle progression from G1 to S phase. Levels of nuclear p27 are reduced in many human cancers. Both the levels and function of p27 are regulated by transcriptional, translational, and posttranslational mechanisms. In regulating p27, posttranslational phosphorylation of the protein is particularly important for determining susceptibility to ubiquitination and proteolytic degradation, as well as the levels, subcellular localization, and functional activity of p27. In addition to the control of cell cycle, cytoplasmic expression of p27 can enhance cell motility, increase renewal of stem cells, inhibit apoptosis, induce autophagy, and stimulate tumor metastasis. Persistence of nuclear p27 provides an independent favorable prognostic factor in many human cancers. Expression or induction of p27 may provide a predictive biomarker for response to chemotherapy, hormonal therapy, and at least some targeted therapies including trastuzumab and Src inhibitors. In addition, restoration of nuclear p27 levels might be achieved pharmacologically, inhibiting proliferation of cancer cells. Inhibition of SKP2-mediated p27 ubiquitination provides one additional promising approach.

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Acknowledgments:

This work was supported in part by a grant CA39930 from the National Cancer Institute, a grant from the Commonwealth Foun-dation (Goodwin Family), and the generous support of the Zarrow Foundation.

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  1. Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    Xiao-Feng Le M.D., Ph.D. & Robert C. Bast Jr M.D.

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  1. M.D. Anderson Cancer Center, University of Texas, Holcombe Blvd. 1515, Houston, 77030, U.S.A.

    Zahid H. Siddik

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Le, XF., Bast, R.C. (2010). p27Kip1 as a Biomarker and Target for Treatment of Cancer. In: Siddik, Z. (eds) Checkpoint Controls and Targets in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60761-178-3_14

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