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p21cip1/waf1 Coordinates Autophagy, Proliferation and Apoptosis in Response to Metabolic Stress

1
Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 169857, Singapore
2
Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA
3
Department of Biochemistry, National University of Singapore, Singapore 117596, Singapore
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(8), 1112; https://doi.org/10.3390/cancers11081112
Received: 24 June 2019 / Revised: 25 July 2019 / Accepted: 30 July 2019 / Published: 3 August 2019
(This article belongs to the Special Issue p21 – An Underestimated Driver for Cancers)
Cancer cells possess metabolic properties that are different from benign cells. These unique characteristics have become attractive targets that are being actively investigated for cancer therapy. p21cip1/waf1, also known as Cyclin-Dependent Kinase inhibitor 1A, is encoded by the CDKN1A gene. It is a major p53 target gene involved in cell cycle progression that has been extensively evaluated. To date, p21 has been reported to regulate various cell functions, both dependent and independent of p53. Besides regulating the cell cycle, p21 also modulates apoptosis, induces senescence, and maintains cellular quiescence in response to various stimuli. p21 transcription is induced in response to stresses, including those from oxidative and chemotherapeutic treatment. A recent study has shown that in response to metabolic stresses such as nutrient and energy depletion, p21 expression is induced to regulate various cell functions. Despite the biological significance, the mechanism of p21 regulation in cancer adaptation to metabolic stress is underexplored and thus represents an exciting field. This review focuses on the recent development of p21 regulation in response to metabolic stress and its impact in inducing cell cycle arrest and death in cancer cells. View Full-Text
Keywords: p21; metabolic stress; cell cycle; autophagy; apoptosis; cancer p21; metabolic stress; cell cycle; autophagy; apoptosis; cancer
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Manu, K.A.; Cao, P.H.A.; Chai, T.F.; Casey, P.J.; Wang, M. p21cip1/waf1 Coordinates Autophagy, Proliferation and Apoptosis in Response to Metabolic Stress. Cancers 2019, 11, 1112.

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