Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.

Anterior Gradient Protein (AGR-2) is reported to be over-expressed in many epithelial cancers and promotes metastasis. A clear-cut mechanism for its observed function(s) has not been previously identified. We found significant upregulation of AGR-2 expression in a bone metastatic prostate cancer cel...

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Autores principales:	Diptiman Chanda, Joo Hyoung Lee, Anandi Sawant, Jonathan A Hensel, Tatyana Isayeva, Stephanie D Reilly, Gene P Siegal, Claire Smith, William Grizzle, Raj Singh, Selvarangan Ponnazhagan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8a7ce2321bd440a78a1264a573ac43dd
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spelling	oai:doaj.org-article:8a7ce2321bd440a78a1264a573ac43dd2021-11-18T08:30:41ZAnterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.1932-620310.1371/journal.pone.0089940https://doaj.org/article/8a7ce2321bd440a78a1264a573ac43dd2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24587138/?tool=EBIhttps://doaj.org/toc/1932-6203Anterior Gradient Protein (AGR-2) is reported to be over-expressed in many epithelial cancers and promotes metastasis. A clear-cut mechanism for its observed function(s) has not been previously identified. We found significant upregulation of AGR-2 expression in a bone metastatic prostate cancer cell line, PC3, following culturing in bone marrow-conditioned medium. Substantial AGR-2 expression was also confirmed in prostate cancer tissue specimens in patients with bone lesions. By developing stable clones of PC3 cells with varying levels of AGR-2 expression, we identified that abrogation of AGR-2 significantly reduced cellular attachment to fibronectin, collagen I, collagen IV, laminin I and fibrinogen. Loss of cellular adhesion was associated with sharp decrease in the expression of α4, α5, αV, β3 and β4 integrins. Failure to undergo apoptosis following detachment is a hallmark of epithelial cancer metastasis. The AGR-2-silenced PC3 cells showed higher resistance to Tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) induced apoptosis in vitro. This observation was also supported by significantly reduced Caspase-3 expression in AGR-2-silenced PC3 cells, which is a key effector of both extrinsic and intrinsic death signaling pathways. These data suggest that AGR-2 influence prostate cancer metastasis by regulation of cellular adhesion and apoptosis.Diptiman ChandaJoo Hyoung LeeAnandi SawantJonathan A HenselTatyana IsayevaStephanie D ReillyGene P SiegalClaire SmithWilliam GrizzleRaj SinghSelvarangan PonnazhaganPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89940 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Diptiman Chanda Joo Hyoung Lee Anandi Sawant Jonathan A Hensel Tatyana Isayeva Stephanie D Reilly Gene P Siegal Claire Smith William Grizzle Raj Singh Selvarangan Ponnazhagan Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.
description	Anterior Gradient Protein (AGR-2) is reported to be over-expressed in many epithelial cancers and promotes metastasis. A clear-cut mechanism for its observed function(s) has not been previously identified. We found significant upregulation of AGR-2 expression in a bone metastatic prostate cancer cell line, PC3, following culturing in bone marrow-conditioned medium. Substantial AGR-2 expression was also confirmed in prostate cancer tissue specimens in patients with bone lesions. By developing stable clones of PC3 cells with varying levels of AGR-2 expression, we identified that abrogation of AGR-2 significantly reduced cellular attachment to fibronectin, collagen I, collagen IV, laminin I and fibrinogen. Loss of cellular adhesion was associated with sharp decrease in the expression of α4, α5, αV, β3 and β4 integrins. Failure to undergo apoptosis following detachment is a hallmark of epithelial cancer metastasis. The AGR-2-silenced PC3 cells showed higher resistance to Tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) induced apoptosis in vitro. This observation was also supported by significantly reduced Caspase-3 expression in AGR-2-silenced PC3 cells, which is a key effector of both extrinsic and intrinsic death signaling pathways. These data suggest that AGR-2 influence prostate cancer metastasis by regulation of cellular adhesion and apoptosis.
format	article
author	Diptiman Chanda Joo Hyoung Lee Anandi Sawant Jonathan A Hensel Tatyana Isayeva Stephanie D Reilly Gene P Siegal Claire Smith William Grizzle Raj Singh Selvarangan Ponnazhagan
author_facet	Diptiman Chanda Joo Hyoung Lee Anandi Sawant Jonathan A Hensel Tatyana Isayeva Stephanie D Reilly Gene P Siegal Claire Smith William Grizzle Raj Singh Selvarangan Ponnazhagan
author_sort	Diptiman Chanda
title	Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.
title_short	Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.
title_full	Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.
title_fullStr	Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.
title_full_unstemmed	Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.
title_sort	anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8a7ce2321bd440a78a1264a573ac43dd
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Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.

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