Evasion of anti-growth signaling: A key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds.
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.
Winship Cancer Institute of Emory University, Atlanta, GA, USA.
A R M Ruhul
ARMR
Amin
Department of Biological Sciences, University of Windsor, 401 Sunset Ave., Room 327, Windsor, Ontario, N9B 3P4, Canada.
Phillip A
PA
Karpowicz
University of Michigan, Ann Arbor, MI, USA.
Thomas E
TE
Carey
Winship Cancer Institute of Emory University, Atlanta, GA, USA; Atlanta Veterans Administration Health Center, Atlanta, GA, USA.
Jack
J
Arbiser
Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Rita
R
Nahta
Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Zhuo G
ZG
Chen
Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Jin-Tang
JT
Dong
Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Omer
O
Kucuk
Henry Ford Hospital, Detroit, MI, USA.
Gazala N
GN
Khan
Albert Einstein College of Medicine, New York, NY, USA.
Gloria S
GS
Huang
Albert Einstein College of Medicine, New York, NY, USA.
Shijun
S
Mi
College of Pharmacy, Seoul National University, Seoul, South Korea.
Ho-Young
HY
Lee
University of the Saarland, Saarbrucken, Germany.
Joerg
J
Reichrath
Nara Medical University, Nara, Japan.
Kanya
K
Honoki
National Technical University of Athens, Athens, Greece.
Alexandros G
AG
Georgakilas
University of Florence, Florence, Italy.
Amedeo
A
Amedei
UAE University, Al Ain, United Arab Emirates; Faculty of Science, Cairo University, Cairo, Egypt.
Amr
A
Amin
University of Illinois at Urbana Champaign, Urbana Champaign, IL, USA.
Bill
B
Helferich
Creighton University, Omaha, USA.
Chandra S
CS
Boosani
University of Rome "Tor Vergata", Rome, Italy.
Maria Rosa
MR
Ciriolo
Ovarian and Prostate Cancer Research Laboratory, Guildford, Surrey, United Kingdom.
Sophie
S
Chen
Purdue University, West Lafayette, IN, USA.
Sulma I
SI
Mohammed
Wayne State University, Detroit, MI, USA.
Asfar S
AS
Azmi
University of Glasgow, Glasgow, United Kingdom.
W Nicol
WN
Keith
School of Chemical and Bio Technology, SASTRA University, Thanjavur, India.
Dipita
D
Bhakta
New York Medical College, Valhalla, NY, USA.
Dorota
D
Halicka
University of Florence, Florence, Italy.
Elena
E
Niccolai
Nara Medical University, Nara, Japan.
Hiromasa
H
Fujii
University of Rome "Tor Vergata", Rome, Italy.
Katia
K
Aquilano
UAE University, Al Ain, United Arab Emirates.
S Salman
SS
Ashraf
Medical Scientist Training Program, Mayo Medical School, Mayo Graduate School, Mayo Clinic, Rochester, MN, USA.
Somaira
S
Nowsheen
University of Illinois at Urbana Champaign, Urbana Champaign, IL, USA.
Xujuan
X
Yang
University of Glasgow, Glasgow, United Kingdom.
Alan
A
Bilsland
Winship Cancer Institute of Emory University, Atlanta, GA, USA. Electronic address: dmshin@emory.edu.
Dong M
DM
Shin
D063646:Carcinogenesis / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D004268:DNA-Binding Proteins; D055436:Growth Differentiation Factor 15 / Q000235:genetics; D000090683:Hippo Signaling Pathway; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D009687:Nuclear Proteins / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D016160:Retinoblastoma Protein / Q000235:genetics; D015398:Signal Transduction; D013002:Somatomedins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D013002:Somatomedins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D017346:Protein Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
Anti-growth signaling; Cancer prevention; Hallmark of cancer; Reversible and irreversible evasion; Tumor suppressor