PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival
BACKGROUND: Proteins that are required for anchorage-independent survival of tumor cells represent attractive targets for therapeutic intervention since this property is believed to be critical for survival of tumor cells displaced from their natural niches. Anchorage-independent survival is induced...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909213/ https://www.ncbi.nlm.nih.gov/pubmed/20668531 http://dx.doi.org/10.1371/journal.pone.0011729 |
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author | Irie, Hanna Y. Shrestha, Yashaswi Selfors, Laura M. Frye, Fabianne Iida, Naoko Wang, Zhigang Zou, Lihua Yao, Jun Lu, Yiling Epstein, Charles B. Natesan, Sridaran Richardson, Andrea L. Polyak, Kornelia Mills, Gordon B. Hahn, William C. Brugge, Joan S. |
author_facet | Irie, Hanna Y. Shrestha, Yashaswi Selfors, Laura M. Frye, Fabianne Iida, Naoko Wang, Zhigang Zou, Lihua Yao, Jun Lu, Yiling Epstein, Charles B. Natesan, Sridaran Richardson, Andrea L. Polyak, Kornelia Mills, Gordon B. Hahn, William C. Brugge, Joan S. |
author_sort | Irie, Hanna Y. |
collection | PubMed |
description | BACKGROUND: Proteins that are required for anchorage-independent survival of tumor cells represent attractive targets for therapeutic intervention since this property is believed to be critical for survival of tumor cells displaced from their natural niches. Anchorage-independent survival is induced by growth factor receptor hyperactivation in many cell types. We aimed to identify molecules that critically regulate IGF-1-induced anchorage-independent survival. METHODS AND RESULTS: We conducted a high-throughput siRNA screen and identified PTK6 as a critical component of IGF-1 receptor (IGF-1R)-induced anchorage-independent survival of mammary epithelial cells. PTK6 downregulation induces apoptosis of breast and ovarian cancer cells deprived of matrix attachment, whereas its overexpression enhances survival. Reverse-phase protein arrays and subsequent analyses revealed that PTK6 forms a complex with IGF-1R and the adaptor protein IRS-1, and modulates anchorage-independent survival by regulating IGF-1R expression and phosphorylation. PTK6 is highly expressed not only in the previously reported Her2(+) breast cancer subtype, but also in high grade ER(+), Luminal B tumors and high expression is associated with adverse outcomes. CONCLUSIONS: These findings highlight PTK6 as a critical regulator of anchorage-independent survival of breast and ovarian tumor cells via modulation of IGF-1 receptor signaling, thus supporting PTK6 as a potential therapeutic target for multiple tumor types. The combined genomic and proteomic approaches in this report provide an effective strategy for identifying oncogenes and their mechanism of action. |
format | Text |
id | pubmed-2909213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-29092132010-07-28 PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival Irie, Hanna Y. Shrestha, Yashaswi Selfors, Laura M. Frye, Fabianne Iida, Naoko Wang, Zhigang Zou, Lihua Yao, Jun Lu, Yiling Epstein, Charles B. Natesan, Sridaran Richardson, Andrea L. Polyak, Kornelia Mills, Gordon B. Hahn, William C. Brugge, Joan S. PLoS One Research Article BACKGROUND: Proteins that are required for anchorage-independent survival of tumor cells represent attractive targets for therapeutic intervention since this property is believed to be critical for survival of tumor cells displaced from their natural niches. Anchorage-independent survival is induced by growth factor receptor hyperactivation in many cell types. We aimed to identify molecules that critically regulate IGF-1-induced anchorage-independent survival. METHODS AND RESULTS: We conducted a high-throughput siRNA screen and identified PTK6 as a critical component of IGF-1 receptor (IGF-1R)-induced anchorage-independent survival of mammary epithelial cells. PTK6 downregulation induces apoptosis of breast and ovarian cancer cells deprived of matrix attachment, whereas its overexpression enhances survival. Reverse-phase protein arrays and subsequent analyses revealed that PTK6 forms a complex with IGF-1R and the adaptor protein IRS-1, and modulates anchorage-independent survival by regulating IGF-1R expression and phosphorylation. PTK6 is highly expressed not only in the previously reported Her2(+) breast cancer subtype, but also in high grade ER(+), Luminal B tumors and high expression is associated with adverse outcomes. CONCLUSIONS: These findings highlight PTK6 as a critical regulator of anchorage-independent survival of breast and ovarian tumor cells via modulation of IGF-1 receptor signaling, thus supporting PTK6 as a potential therapeutic target for multiple tumor types. The combined genomic and proteomic approaches in this report provide an effective strategy for identifying oncogenes and their mechanism of action. Public Library of Science 2010-07-23 /pmc/articles/PMC2909213/ /pubmed/20668531 http://dx.doi.org/10.1371/journal.pone.0011729 Text en Irie 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 Irie, Hanna Y. Shrestha, Yashaswi Selfors, Laura M. Frye, Fabianne Iida, Naoko Wang, Zhigang Zou, Lihua Yao, Jun Lu, Yiling Epstein, Charles B. Natesan, Sridaran Richardson, Andrea L. Polyak, Kornelia Mills, Gordon B. Hahn, William C. Brugge, Joan S. PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival |
title | PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival |
title_full | PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival |
title_fullStr | PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival |
title_full_unstemmed | PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival |
title_short | PTK6 Regulates IGF-1-Induced Anchorage-Independent Survival |
title_sort | ptk6 regulates igf-1-induced anchorage-independent survival |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909213/ https://www.ncbi.nlm.nih.gov/pubmed/20668531 http://dx.doi.org/10.1371/journal.pone.0011729 |
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