The Large GTPase, GBP-2, Regulates Rho Family GTPases to Inhibit Migration and Invadosome Formation in Breast Cancer Cells

Breast cancer is the most common cancer in women. Despite advances in early detection and treatment, it is predicted that over 43,000 women will die of breast cancer in 2021. To lower this number, more information about the molecular players in breast cancer are needed. Guanylate-Binding Protein-2 h...

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Autores principales: Geoffrey O. Nyabuto, John P. Wilson, Samantha A. Heilman, Ryan C. Kalb, Jonathan P. Kopacz, Ankita V. Abnave, Deborah J. Vestal
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:7d6693cec90c42a3ac04831a12671b8c2021-11-25T17:01:53ZThe Large GTPase, GBP-2, Regulates Rho Family GTPases to Inhibit Migration and Invadosome Formation in Breast Cancer Cells10.3390/cancers132256322072-6694https://doaj.org/article/7d6693cec90c42a3ac04831a12671b8c2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5632https://doaj.org/toc/2072-6694Breast cancer is the most common cancer in women. Despite advances in early detection and treatment, it is predicted that over 43,000 women will die of breast cancer in 2021. To lower this number, more information about the molecular players in breast cancer are needed. Guanylate-Binding Protein-2 has been correlated with better prognosis in breast cancer. In this study, we asked if the expression of GBP-2 in breast cancer merely provided a biomarker for improved prognosis or whether it actually contributed to improving outcome. To answer this, the 4T1 model of murine breast cancer was used. 4T1 cells themselves are highly aggressive and highly metastatic, while 67NR cells, isolated from the same tumor, do not leave the primary site. The expression of GBP-2 was examined in the two cell lines and found to be inversely correlated with aggressiveness/metastasis. Proliferation, migration, and invadosome formation were analyzed after altering the expression levels of GBP-2. Our experiments show that GBP-2 does not alter the proliferation of these cells but inhibits migration and invadosome formation downstream of regulation of Rho GTPases. Together these data demonstrate that GBP-2 is responsible for cell autonomous activities that make breast cancer cells less aggressive.Geoffrey O. NyabutoJohn P. WilsonSamantha A. HeilmanRyan C. KalbJonathan P. KopaczAnkita V. AbnaveDeborah J. VestalMDPI AGarticleGTPasebreast cancerGuanylate-Binding ProteininvadosomemigrationcytoskeletonNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5632, p 5632 (2021)
institution DOAJ
collection DOAJ
language EN
topic GTPase
breast cancer
Guanylate-Binding Protein
invadosome
migration
cytoskeleton
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle GTPase
breast cancer
Guanylate-Binding Protein
invadosome
migration
cytoskeleton
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Geoffrey O. Nyabuto
John P. Wilson
Samantha A. Heilman
Ryan C. Kalb
Jonathan P. Kopacz
Ankita V. Abnave
Deborah J. Vestal
The Large GTPase, GBP-2, Regulates Rho Family GTPases to Inhibit Migration and Invadosome Formation in Breast Cancer Cells
description Breast cancer is the most common cancer in women. Despite advances in early detection and treatment, it is predicted that over 43,000 women will die of breast cancer in 2021. To lower this number, more information about the molecular players in breast cancer are needed. Guanylate-Binding Protein-2 has been correlated with better prognosis in breast cancer. In this study, we asked if the expression of GBP-2 in breast cancer merely provided a biomarker for improved prognosis or whether it actually contributed to improving outcome. To answer this, the 4T1 model of murine breast cancer was used. 4T1 cells themselves are highly aggressive and highly metastatic, while 67NR cells, isolated from the same tumor, do not leave the primary site. The expression of GBP-2 was examined in the two cell lines and found to be inversely correlated with aggressiveness/metastasis. Proliferation, migration, and invadosome formation were analyzed after altering the expression levels of GBP-2. Our experiments show that GBP-2 does not alter the proliferation of these cells but inhibits migration and invadosome formation downstream of regulation of Rho GTPases. Together these data demonstrate that GBP-2 is responsible for cell autonomous activities that make breast cancer cells less aggressive.
format article
author Geoffrey O. Nyabuto
John P. Wilson
Samantha A. Heilman
Ryan C. Kalb
Jonathan P. Kopacz
Ankita V. Abnave
Deborah J. Vestal
author_facet Geoffrey O. Nyabuto
John P. Wilson
Samantha A. Heilman
Ryan C. Kalb
Jonathan P. Kopacz
Ankita V. Abnave
Deborah J. Vestal
author_sort Geoffrey O. Nyabuto
title The Large GTPase, GBP-2, Regulates Rho Family GTPases to Inhibit Migration and Invadosome Formation in Breast Cancer Cells
title_short The Large GTPase, GBP-2, Regulates Rho Family GTPases to Inhibit Migration and Invadosome Formation in Breast Cancer Cells
title_full The Large GTPase, GBP-2, Regulates Rho Family GTPases to Inhibit Migration and Invadosome Formation in Breast Cancer Cells
title_fullStr The Large GTPase, GBP-2, Regulates Rho Family GTPases to Inhibit Migration and Invadosome Formation in Breast Cancer Cells
title_full_unstemmed The Large GTPase, GBP-2, Regulates Rho Family GTPases to Inhibit Migration and Invadosome Formation in Breast Cancer Cells
title_sort large gtpase, gbp-2, regulates rho family gtpases to inhibit migration and invadosome formation in breast cancer cells
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/7d6693cec90c42a3ac04831a12671b8c
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