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Review
. 2015 Dec:35 Suppl:S55-S77.
doi: 10.1016/j.semcancer.2015.02.005. Epub 2015 Mar 6.

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

A R M Ruhul Amin  1 , Phillip A Karpowicz  2 , Thomas E Carey  3 , Jack Arbiser  4 , Rita Nahta  1 , Zhuo G Chen  1 , Jin-Tang Dong  1 , Omer Kucuk  1 , Gazala N Khan  5 , Gloria S Huang  6 , Shijun Mi  6 , Ho-Young Lee  7 , Joerg Reichrath  8 , Kanya Honoki  9 , Alexandros G Georgakilas  10 , Amedeo Amedei  11 , Amr Amin  12 , Bill Helferich  13 , Chandra S Boosani  14 , Maria Rosa Ciriolo  15 , Sophie Chen  16 , Sulma I Mohammed  17 , Asfar S Azmi  18 , W Nicol Keith  19 , Dipita Bhakta  20 , Dorota Halicka  21 , Elena Niccolai  11 , Hiromasa Fujii  9 , Katia Aquilano  15 , S Salman Ashraf  22 , Somaira Nowsheen  23 , Xujuan Yang  13 , Alan Bilsland  19 , Dong M Shin  24
Affiliations
Review

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

A R M Ruhul Amin et al. Semin Cancer Biol. 2015 Dec.

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.

Keywords: Anti-growth signaling; Cancer prevention; Hallmark of cancer; Reversible and irreversible evasion; Tumor suppressor.

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Figures

Figure 1
Figure 1
Mechanism of evasion of tumor suppressor pathways and their targeting by natural compounds.
Figure 2
Figure 2
Cyclin D1 and p16 regulate cell cycle entry. When p16 is lost, CDK inhibitors can restore function.
Figure 3
Figure 3
HPV-E7 binds to Rb blocking it from inactivating E2F. E2F upregulates both cell cycle genes and p16 making it a marker for HPV induced cancers.
Figure 4
Figure 4
Hippo signaling inhibits YAP/TAZ-mediated activation of genes involved in proliferation and survival.
See this image and copyright information in PMC

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