Evasion of anti-growth signaling: A key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds.

Winship Cancer Institute of Emory University, Atlanta, GA, USA. Department of Biological Sciences, University of Windsor, 401 Sunset Ave., Room 327, Windsor, Ontario, N9B 3P4, Canada. University of Michigan, Ann Arbor, MI, USA. Winship Cancer Institute of Emory University, Atlanta, GA, USA; Atlanta Veterans Administration Health Center, Atlanta, GA, USA. Henry Ford Hospital, Detroit, MI, USA. Albert Einstein College of Medicine, New York, NY, USA. College of Pharmacy, Seoul National University, Seoul, South Korea. University of the Saarland, Saarbrucken, Germany. Nara Medical University, Nara, Japan. National Technical University of Athens, Athens, Greece. University of Florence, Florence, Italy. UAE University, Al Ain, United Arab Emirates; Faculty of Science, Cairo University, Cairo, Egypt. University of Illinois at Urbana Champaign, Urbana Champaign, IL, USA. Creighton University, Omaha, USA. University of Rome "Tor Vergata", Rome, Italy. Ovarian and Prostate Cancer Research Laboratory, Guildford, Surrey, United Kingdom. Purdue University, West Lafayette, IN, USA. Wayne State University, Detroit, MI, USA. University of Glasgow, Glasgow, United Kingdom. School of Chemical and Bio Technology, SASTRA University, Thanjavur, India. New York Medical College, Valhalla, NY, USA. UAE University, Al Ain, United Arab Emirates. Medical Scientist Training Program, Mayo Medical School, Mayo Graduate School, Mayo Clinic, Rochester, MN, USA. Winship Cancer Institute of Emory University, Atlanta, GA, USA. Electronic address: dmshin@emory.edu.

Seminars in cancer biology. 2015;:S55-S77
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Abstract

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting.

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Publication Type : Review

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