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Therapeutic Implications of GIPC1 Silencing in Cancer
GIPC1 is a cytoplasmic scaffold protein that interacts with numerous receptor signaling complexes, and emerging evidence suggests that it plays a role in tumorigenesis. GIPC1 is highly expressed in a number of human malignancies, including breast, ovarian, gastric, and pancreatic cancers. Suppressio...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012716/ https://www.ncbi.nlm.nih.gov/pubmed/21209904 http://dx.doi.org/10.1371/journal.pone.0015581 |
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author | Chittenden, Thomas W. Pak, Jane Rubio, Renee Cheng, Hailing Holton, Kristina Prendergast, Niall Glinskii, Vladimir Cai, Yi Culhane, Aedin Bentink, Stefan Schwede, Mathew Mar, Jessica C. Howe, Eleanor A. Aryee, Martin Sultana, Razvan Lanahan, Anthony A. Taylor, Jennifer M. Holmes, Chris Hahn, William C. Zhao, Jean J. Iglehart, J. Dirk Quackenbush, John |
author_facet | Chittenden, Thomas W. Pak, Jane Rubio, Renee Cheng, Hailing Holton, Kristina Prendergast, Niall Glinskii, Vladimir Cai, Yi Culhane, Aedin Bentink, Stefan Schwede, Mathew Mar, Jessica C. Howe, Eleanor A. Aryee, Martin Sultana, Razvan Lanahan, Anthony A. Taylor, Jennifer M. Holmes, Chris Hahn, William C. Zhao, Jean J. Iglehart, J. Dirk Quackenbush, John |
author_sort | Chittenden, Thomas W. |
collection | PubMed |
description | GIPC1 is a cytoplasmic scaffold protein that interacts with numerous receptor signaling complexes, and emerging evidence suggests that it plays a role in tumorigenesis. GIPC1 is highly expressed in a number of human malignancies, including breast, ovarian, gastric, and pancreatic cancers. Suppression of GIPC1 in human pancreatic cancer cells inhibits in vivo tumor growth in immunodeficient mice. To better understand GIPC1 function, we suppressed its expression in human breast and colorectal cancer cell lines and human mammary epithelial cells (HMECs) and assayed both gene expression and cellular phenotype. Suppression of GIPC1 promotes apoptosis in MCF-7, MDA-MD231, SKBR-3, SW480, and SW620 cells and impairs anchorage-independent colony formation of HMECs. These observations indicate GIPC1 plays an essential role in oncogenic transformation, and its expression is necessary for the survival of human breast and colorectal cancer cells. Additionally, a GIPC1 knock-down gene signature was used to interrogate publically available breast and ovarian cancer microarray datasets. This GIPC1 signature statistically correlates with a number of breast and ovarian cancer phenotypes and clinical outcomes, including patient survival. Taken together, these data indicate that GIPC1 inhibition may represent a new target for therapeutic development for the treatment of human cancers. |
format | Text |
id | pubmed-3012716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30127162011-01-05 Therapeutic Implications of GIPC1 Silencing in Cancer Chittenden, Thomas W. Pak, Jane Rubio, Renee Cheng, Hailing Holton, Kristina Prendergast, Niall Glinskii, Vladimir Cai, Yi Culhane, Aedin Bentink, Stefan Schwede, Mathew Mar, Jessica C. Howe, Eleanor A. Aryee, Martin Sultana, Razvan Lanahan, Anthony A. Taylor, Jennifer M. Holmes, Chris Hahn, William C. Zhao, Jean J. Iglehart, J. Dirk Quackenbush, John PLoS One Research Article GIPC1 is a cytoplasmic scaffold protein that interacts with numerous receptor signaling complexes, and emerging evidence suggests that it plays a role in tumorigenesis. GIPC1 is highly expressed in a number of human malignancies, including breast, ovarian, gastric, and pancreatic cancers. Suppression of GIPC1 in human pancreatic cancer cells inhibits in vivo tumor growth in immunodeficient mice. To better understand GIPC1 function, we suppressed its expression in human breast and colorectal cancer cell lines and human mammary epithelial cells (HMECs) and assayed both gene expression and cellular phenotype. Suppression of GIPC1 promotes apoptosis in MCF-7, MDA-MD231, SKBR-3, SW480, and SW620 cells and impairs anchorage-independent colony formation of HMECs. These observations indicate GIPC1 plays an essential role in oncogenic transformation, and its expression is necessary for the survival of human breast and colorectal cancer cells. Additionally, a GIPC1 knock-down gene signature was used to interrogate publically available breast and ovarian cancer microarray datasets. This GIPC1 signature statistically correlates with a number of breast and ovarian cancer phenotypes and clinical outcomes, including patient survival. Taken together, these data indicate that GIPC1 inhibition may represent a new target for therapeutic development for the treatment of human cancers. Public Library of Science 2010-12-30 /pmc/articles/PMC3012716/ /pubmed/21209904 http://dx.doi.org/10.1371/journal.pone.0015581 Text en Chittenden et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Chittenden, Thomas W. Pak, Jane Rubio, Renee Cheng, Hailing Holton, Kristina Prendergast, Niall Glinskii, Vladimir Cai, Yi Culhane, Aedin Bentink, Stefan Schwede, Mathew Mar, Jessica C. Howe, Eleanor A. Aryee, Martin Sultana, Razvan Lanahan, Anthony A. Taylor, Jennifer M. Holmes, Chris Hahn, William C. Zhao, Jean J. Iglehart, J. Dirk Quackenbush, John Therapeutic Implications of GIPC1 Silencing in Cancer |
title | Therapeutic Implications of GIPC1 Silencing in Cancer |
title_full | Therapeutic Implications of GIPC1 Silencing in Cancer |
title_fullStr | Therapeutic Implications of GIPC1 Silencing in Cancer |
title_full_unstemmed | Therapeutic Implications of GIPC1 Silencing in Cancer |
title_short | Therapeutic Implications of GIPC1 Silencing in Cancer |
title_sort | therapeutic implications of gipc1 silencing in cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012716/ https://www.ncbi.nlm.nih.gov/pubmed/21209904 http://dx.doi.org/10.1371/journal.pone.0015581 |
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