Evasion of anti-growth signaling: A key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds.
Amin ARMR, Karpowicz PA, Carey TE, Arbiser J, Nahta R, Chen ZG, Dong JT, Kucuk O, Khan GN, Huang GS, Mi S, Lee HY, Reichrath J, Honoki K, Georgakilas AG, Amedei A, Amin A, Helferich B, Boosani CS, Ciriolo MR, Chen S, Mohammed SI, Azmi AS, Keith WN, Bhakta D, Halicka D, Niccolai E, Fujii H, Aquilano K, Ashraf SS, Nowsheen S, Yang X, Bilsland A, Shin DM. Evasion of anti-growth signaling: A key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds. Semin Cancer Biol. 2015 Dec;35 Suppl:S55-S77.
Seminars in cancer biology
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.
Medical Subject Headings
Carcinogenesis; Cell Proliferation; Growth Differentiation Factor 15; Humans; Kruppel-Like Transcription Factors; Molecular Targeted Therapy; Neoplasms; Nuclear Proteins; PTEN Phosphohydrolase; Protein-Serine-Threonine Kinases; Retinoblastoma Protein; Signal Transduction; Somatomedins; Transcription Factors; Tumor Suppressor Protein p53