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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...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
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.
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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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