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Sci. STKE, 20 January 2004
Vol. 2004, Issue 216, p. re2
[DOI: 10.1126/stke.2162004re2]


G Proteins in Cancer: The Prostate Cancer Paradigm

Yehia Daaka*

Department of Surgery and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.

Gloss: This STKE Review discusses molecular signaling pathways that contribute to prostate cancer progression. With 5 figures, 2 tables, and 112 citations, the article provides an in-depth analysis of the role of heterotrimeric guanine nucleotide-binding proteins (G proteins) in stimulating androgen-independent growth of prostate cancer cells. Many of the proposed pathways that contribute to androgen-independent cell proliferation appear to involve the extracellular signal-regulated kinase 1 and 2 (ERKs). G proteins may be activated in response to excessive ligand production for their receptors and may subsequently activate growth factor receptors that themselves activate ERKs, or they may promote the androgen-independent activation of androgen receptors.

Contact information. DUMC 2607, Duke University Medical Center, Durham, NC 27710, USA. Telephone, 919-684-8440; fax, 919-684-9990; e-mail, daaka001{at}

Citation: Y. Daaka, G Proteins in Cancer: The Prostate Cancer Paradigm. Sci. STKE 2004, re2 (2004).

G Protein-Coupled Receptor-Mediated Activation of p110{beta} by G{beta}{gamma} Is Required for Cellular Transformation and Invasiveness.
H. A. Dbouk, O. Vadas, A. Shymanets, J. E. Burke, R. S. Salamon, B. D. Khalil, M. O. Barrett, G. L. Waldo, C. Surve, C. Hsueh, et al. (2012)
Science Signaling 5, ra89
   Abstract »    Full Text »    PDF »
Dissection of Aberrant GPCR Signaling in Tumorigenesis - A Systems Biology Approach.
J. Wu, N. Xie, X. Zhao, E. C. Nice, and C. Huang (2012)
Cancer Genomics Proteomics 9, 37-50
   Abstract »    Full Text »    PDF »
Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer.
P. Gazzerro, M. C. Proto, G. Gangemi, A. M. Malfitano, E. Ciaglia, S. Pisanti, A. Santoro, C. Laezza, and M. Bifulco (2012)
Pharmacol. Rev. 64, 102-146
   Abstract »    Full Text »    PDF »
Disease-associated GPR56 Mutations Cause Bilateral Frontoparietal Polymicrogyria via Multiple Mechanisms.
N.-Y. Chiang, C.-C. Hsiao, Y.-S. Huang, H.-Y. Chen, I.-J. Hsieh, G.-W. Chang, and H.-H. Lin (2011)
J. Biol. Chem. 286, 14215-14225
   Abstract »    Full Text »    PDF »
G{beta}{gamma} Signaling Promotes Breast Cancer Cell Migration and Invasion.
J. K. Kirui, Y. Xie, D. W. Wolff, H. Jiang, P. W. Abel, and Y. Tu (2010)
J. Pharmacol. Exp. Ther. 333, 393-403
   Abstract »    Full Text »    PDF »
Critical Role of G{alpha}12 and G{alpha}13 for Human Small Cell Lung Cancer Cell Proliferation In vitro and Tumor Growth In vivo.
M. Grzelinski, O. Pinkenburg, T. Buch, M. Gold, S. Stohr, H. Kalwa, T. Gudermann, and A. Aigner (2010)
Clin. Cancer Res. 16, 1402-1415
   Abstract »    Full Text »    PDF »
Identification of {beta}Arrestin2 as a corepressor of androgen receptor signaling in prostate cancer.
V. Lakshmikanthan, L. Zou, J. I. Kim, A. Michal, Z. Nie, N. C. Messias, J. L. Benovic, and Y. Daaka (2009)
PNAS 106, 9379-9384
   Abstract »    Full Text »    PDF »
The Glutamatergic System Expression in Human PC-3 and LNCaP Prostate Cancer Cells.
Anticancer Res 29, 371-377
   Abstract »    Full Text »    PDF »
2,2-Bis(4-Chlorophenyl)-1,1-Dichloroethylene Stimulates Androgen Independence in Prostate Cancer Cells through Combinatorial Activation of Mutant Androgen Receptor and Mitogen-Activated Protein Kinase Pathways.
S. Shah, J. K. Hess-Wilson, S. Webb, H. Daly, S. Godoy-Tundidor, J. Kim, J. Boldison, Y. Daaka, and K. E. Knudsen (2008)
Mol. Cancer Res. 6, 1507-1520
   Abstract »    Full Text »    PDF »
Vasoactive Intestinal Peptide Transactivates the Androgen Receptor through a Protein Kinase A-Dependent Extracellular Signal-Regulated Kinase Pathway in Prostate Cancer LNCaP Cells.
Y. Xie, D. W. Wolff, M.-F. Lin, and Y. Tu (2007)
Mol. Pharmacol. 72, 73-85
   Abstract »    Full Text »    PDF »
Ligand Binding to the Androgen Receptor Induces Conformational Changes That Regulate Phosphatase Interactions.
C.-S. Yang, H.-W. Xin, J. B. Kelley, A. Spencer, D. L. Brautigan, and B. M. Paschal (2007)
Mol. Cell. Biol. 27, 3390-3404
   Abstract »    Full Text »    PDF »
Differential targeting of Gbetagamma-subunit signaling with small molecules..
T. M. Bonacci, J. L. Mathews, C. Yuan, D. M. Lehmann, S. Malik, D. Wu, J. L. Font, J. M. Bidlack, and A. V. Smrcka (2006)
Science 312, 443-446
   Abstract »    Full Text »    PDF »
Targeting Multiple Signaling Pathways as a Strategy for Managing Prostate Cancer: Multifocal Signal Modulation Therapy.
M. F. McCarty (2004)
Integr Cancer Ther 3, 349-380
   Abstract »    PDF »
Finding fusion genes resulting from chromosome rearrangement by analyzing the expressed sequence databases.
Y. Hahn, T. K. Bera, K. Gehlhaus, I. R. Kirsch, I. H. Pastan, and B. Lee (2004)
PNAS 101, 13257-13261
   Abstract »    Full Text »    PDF »

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