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

• Type of Material: Article
• Authors: A.R.M. Amin, Emory University; Phillip A. Karpowicz, University of Windsor; Thomas E. Carey, University of Michigan; Jack Arbiser, Emory University; Rita Nahta, Emory University; Georgia Chen, Emory University; Jin-Tang Dong, Emory University; Omer Kucuk, Emory University; Gazala N. Khan, Henry Ford Hospital; Gloria S. Huang, Albert Einstein Coll Med; Shijun Mi, Albert Einstein Coll Med; Ho-Young Lee, Seoul Natl Univ; Joerg Reichrath, Saarland University; Kanya Honoki, Nara Medical University; Alexandros G. Georgakilas, Natl Tech Univ Athens; Amedeo Amedei, University of Florence; Amr Amin, Univ Illinois; Bill Helferich, Creighton University; Chandra S. Boosani, Univ Roma Tor Vergata; Maria Rosa Ciriolo, Purdue University; Sophie Chen, Wayne State University; Sulma I. Mohammed, University of Glasgow; Asfar S. Azmi, SASTRA Univ; W. Nicol Keith, New York Medical College; Dipita Bhakta, Nara Medical University; Dorota Halicka, Univ Roma Tor Vergata; Elena Niccolai, UAE Univ; Hiromasa Fujii, Mayo Clinic; Katia Aquilano, Univ Illinois; S. Salman Ashraf, University of Glasgow; Somaira Nowsheen, Emory University; Xujuan Yang; Alan Bilsland; Dong Shin
• Language: English
• Date: 2015-12-01
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.semcancer.2015.02.005
• Title of Journal or Parent Work: Seminars in Cancer Biology
• ISSN: 1044-579X
• Volume: 35
• Start Page: S55
• End Page: S77
• Keywords: Life Sciences & Biomedicine; Reversible and irreversible evasion; Anti-growth signaling; Hallmark of cancer; Cancer prevention; Oncology; Tumor suppressor; Science & Technology
• Research Categories: Health Sciences, Oncology; Health Sciences, Pharmacology

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.