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August 2012 Volume 28 Issue 2

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International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

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Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

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Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

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Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

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Article

Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the proliferation and invasion of human prostate cancer cells in vitro through suppression of Ras activation

  • Authors:
    • Wenjuan Yu
    • Yuewei Wang
    • Miaozi Gong
    • Fei Pei
    • Jie Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, P.R. China, Department of Vascular Surgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, P.R. China, Department of Pathology, Health Science Center, Peking University, Beijing, P.R. China
  • Pages: 606-614
    |
    Published online on: June 1, 2012
       https://doi.org/10.3892/or.2012.1848
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Abstract

Phosphoprotein associated with glycosphingolipid microdomains 1 (PAG) is an important negative regulator of immune signaling in T lymphocytes. However, newly emerging evidence has indicated that PAG may play important roles in tumor cells. Our previously reported cDNA microarray experiments identified PAG as a gene down-regulated in the high metastatic potential prostate cancer cell line PC-3M-1E8. In this study, we investigated the role of PAG in the proliferation, invasion and metastasis of prostate cancer cells and the underlying mechanisms. We confirmed that the expression of PAG at both the mRNA and protein levels was low in PC-3M-1E8 and DU145 cells compared to low metastatic potential prostate cancer cells PC-3M-2B4. In addition, we demonstrated that the reintroduction of PAG to PC-3M-1E8 and DU145 cells led to reduced proliferation through cell cycle arrest, decreased anchorage-independent growth and reduced invasion ability of tumor cells in vitro. This is the first report demonstrating that PAG inhibits the proliferation and invasion potential of prostate cancer cells via the interaction with RasGAP to recruit RasGAP to the cell membrane, where RasGAP hydrolyzes GTP to GDP, reduces the level of activated Ras, and ultimately suppresses the activation of ERK1/2, cyclin D1 and other effectors of the Ras signaling pathway. Morphologically, we observed that PAG could diminish the formation of pseudopodia on the cell surface and redistribute the intracellular F-actin in PC-3M-1E8 cells, which directly leads to the decreased invasion and metastasis potential of tumor cells. Taken together, these results suggest that PAG acts to inhibit the development and metastasis of prostate cancers and represents a novel therapeutic target for prostate cancer.
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View References

1 

Liu YX, Zheng J and Fang WG: Isolation and characterization of human prostate cancer cell subclones with different metastatic potential. Chin J Pathol. 28:361–364. 1999.PubMed/NCBI

2 

Svec A: Phosphoprotein associated with glycosphingolipid-enriched microdomains/Csk-binding protein: a protein that matters. Pathol Res Pract. 204:785–792. 2008. View Article : Google Scholar

3 

Brdickova N, Brdicka T, Andera L, Spicka J, Angelisova P, Milgram SL and Horejsi V: Interaction between two adapter proteins, PAG and EBP50: a possible link between membrane rafts and actin cytoskeleton. FEBS Lett. 507:133–136. 2001. View Article : Google Scholar

4 

Kawabuchi M, Satomi Y, Takao T, Shimonishi Y, Nada S, Nagai K, Tarakhovsky A and Okada M: Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases. Nature. 404:999–1003. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Takeuchi S, Takayama Y, Ogawa A, Tamura K and Okada M: Transmembrane phosphoprotein cbp positively regulates the activity of the carboxyl-terminal src kinase Csk. J Biol Chem. 275:29183–29186. 2000. View Article : Google Scholar : PubMed/NCBI

6 

Brdicka T, Pavlistova D, Leo A, Bruyns E, Korinek V, Angelisova P, Scherer J, Shevchenko A, Hilgert I, Cerny J, Drbal K, Kuramitsu Y, Kornacker B, Horejsi V and Schraven B: Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation. J Exp Med. 191:1591–1604. 2000. View Article : Google Scholar

7 

Torgersen KM, Vang T, Abrahamsen H, Yaqub S, Horejsi V, Schraven B, Rolstad B, Mustelin T and Tasken K: Release from tonic inhibition of T cell activation through transient displacement of C-terminal Src kinase (Csk) from lipid rafts. J Biol Chem. 276:29313–29318. 2001. View Article : Google Scholar

8 

Jiang LQ, Feng X, Zhou W, Knyazev PG, Ullrich A and Chen Z: Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src activation. Oncogene. 25:5495–5506. 2006. View Article : Google Scholar

9 

Smida M, Posevitz-Fejfar A, Horejsi V, Schraven B and Lindquist JA: A novel negative regulatory function of the phosphoprotein associated with glycosphingolipid-enriched microdomains: blocking Ras activation. Blood. 110:596–615. 2007. View Article : Google Scholar

10 

Durrheim GA, Garnett D, Dennehy KM and Beyers AD: Thy-1 associated pp85–90 is a potential docking site for SH2 domain-containing signal transduction molecules. Cell Biol Int. 25:33–42. 2001.PubMed/NCBI

11 

Sanchez-Margalet V and Najib S: Sam68 is a docking protein linking GAP and PI3K in insulin receptor signaling. Mol Cell Endocrinol. 183:113–121. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Huang KT, Chen YH and Walker AM: Inaccuracies in MTS assays: major distorting effects of medium, serum albumin, and fatty acids. Biotechniques. 37:406–412. 2004.PubMed/NCBI

13 

Simeoni L, Smida M, Posevitz V, Schraven B and Lindquist JA: Right time, right place: the organization of membrane proximal signaling. Semin Immunol. 17:35–49. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Cloutier JF, Chow LM and Veillette A: Requirement of the SH3 and SH2 domains for the inhibitory function of tyrosine protein kinase p50csk in T lymphocytes. Mol Cell Biol. 15:5937–5944. 1995.

15 

Itoh K, Sakakibara M, Yamasaki S, Takeuchi A, Arase H, Miyazaki M, Nakajima N, Okada M and Saito T: Cutting edge: negative regulation of immune synapse formation by anchoring lipid raft to cytoskeleton through Cbp-EBP50-ERM assembly. J Immunol. 168:541–544. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Harder T and Simons K: Clusters of glycolipid and glycosylphosph atidylinositol-anchored proteins in lymphoid cells: accumulation of actin regulated by local tyrosine phosphorylation. Eur J Immunol. 29:556–562. 1999. View Article : Google Scholar

17 

Condeelis JS, Wyckoff JB, Bailly M, Pestell R, Lawrence D, Backer J and Segall JE: Lamellipodia in invasion. Semin Cancer Biol. 11:119–128. 2001. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yu W, Wang Y, Gong M, Pei F and Zheng J: Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the proliferation and invasion of human prostate cancer cells in vitro through suppression of Ras activation. Oncol Rep 28: 606-614, 2012.
APA
Yu, W., Wang, Y., Gong, M., Pei, F., & Zheng, J. (2012). Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the proliferation and invasion of human prostate cancer cells in vitro through suppression of Ras activation. Oncology Reports, 28, 606-614. https://doi.org/10.3892/or.2012.1848
MLA
Yu, W., Wang, Y., Gong, M., Pei, F., Zheng, J."Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the proliferation and invasion of human prostate cancer cells in vitro through suppression of Ras activation". Oncology Reports 28.2 (2012): 606-614.
Chicago
Yu, W., Wang, Y., Gong, M., Pei, F., Zheng, J."Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the proliferation and invasion of human prostate cancer cells in vitro through suppression of Ras activation". Oncology Reports 28, no. 2 (2012): 606-614. https://doi.org/10.3892/or.2012.1848
Copy and paste a formatted citation
x
Spandidos Publications style
Yu W, Wang Y, Gong M, Pei F and Zheng J: Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the proliferation and invasion of human prostate cancer cells in vitro through suppression of Ras activation. Oncol Rep 28: 606-614, 2012.
APA
Yu, W., Wang, Y., Gong, M., Pei, F., & Zheng, J. (2012). Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the proliferation and invasion of human prostate cancer cells in vitro through suppression of Ras activation. Oncology Reports, 28, 606-614. https://doi.org/10.3892/or.2012.1848
MLA
Yu, W., Wang, Y., Gong, M., Pei, F., Zheng, J."Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the proliferation and invasion of human prostate cancer cells in vitro through suppression of Ras activation". Oncology Reports 28.2 (2012): 606-614.
Chicago
Yu, W., Wang, Y., Gong, M., Pei, F., Zheng, J."Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the proliferation and invasion of human prostate cancer cells in vitro through suppression of Ras activation". Oncology Reports 28, no. 2 (2012): 606-614. https://doi.org/10.3892/or.2012.1848
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