Wnt5A modulates integrin expression in a receptor-dependent manner in ovarian cancer cells

Abstract Wnt5A signals through various receptors that confer versatile biological functions. Here, we used Wnt5A overexpressing human ovarian SKOV-3 and OVCAR-3 stable clones for assessing integrin expression, cell proliferation, migration, invasion, and the ability of multicellular aggregates (MCAs...

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Autores principales: Vajihe Azimian-Zavareh, Zeinab Dehghani-Ghobadi, Marzieh Ebrahimi, Kian Mirzazadeh, Irina Nazarenko, Ghamartaj Hossein
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/b7767adc982e415e8a35af79b5a07103
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spelling oai:doaj.org-article:b7767adc982e415e8a35af79b5a071032021-12-02T17:05:46ZWnt5A modulates integrin expression in a receptor-dependent manner in ovarian cancer cells10.1038/s41598-021-85356-62045-2322https://doaj.org/article/b7767adc982e415e8a35af79b5a071032021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85356-6https://doaj.org/toc/2045-2322Abstract Wnt5A signals through various receptors that confer versatile biological functions. Here, we used Wnt5A overexpressing human ovarian SKOV-3 and OVCAR-3 stable clones for assessing integrin expression, cell proliferation, migration, invasion, and the ability of multicellular aggregates (MCAs) formation. We found here, that Wnt5A regulates differently the expression of its receptors in the stable Wnt5A overexpressing clones. The expression levels of Frizzled (FZD)-2 and -5, were increased in different clones. However ROR-1, -2 expression levels were differently regulated in clones. Wnt5A overexpressing clones showed increased cell proliferation, migration, and clonogenicity. Moreover, Wnt5A overexpressing SKOV-3 clone showed increased MCAs formation ability. Cell invasion had been increased in OVCAR-3-derived clones, while this was decreased in SKOV-3-derived clone. Importantly, αv integrin expression levels were increased in all assessed clones, accompanied by increased cell attachment to fibronectin and focal adhesion kinase activity. Moreover, the treatment of clones with Box5 as a Wnt5A/FZD5 antagonist abrogates ITGAV increase, cell proliferation, migration, and their attachment to fibronectin. Accordingly, we observed significantly higher expression levels of ITGAV and ITGB3 in human high-grade serous ovarian cancer specimens and ITGAV correlated positively with Wnt5A in metastatic serous type ovarian cancer. In summary, we hypothesize here, that Wnt5A/FZD-5 signaling modulate αv integrin expression levels that could be associated with ovarian cancer cell proliferation, migration, and fibronectin attachment.Vajihe Azimian-ZavarehZeinab Dehghani-GhobadiMarzieh EbrahimiKian MirzazadehIrina NazarenkoGhamartaj HosseinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Vajihe Azimian-Zavareh
Zeinab Dehghani-Ghobadi
Marzieh Ebrahimi
Kian Mirzazadeh
Irina Nazarenko
Ghamartaj Hossein
Wnt5A modulates integrin expression in a receptor-dependent manner in ovarian cancer cells
description Abstract Wnt5A signals through various receptors that confer versatile biological functions. Here, we used Wnt5A overexpressing human ovarian SKOV-3 and OVCAR-3 stable clones for assessing integrin expression, cell proliferation, migration, invasion, and the ability of multicellular aggregates (MCAs) formation. We found here, that Wnt5A regulates differently the expression of its receptors in the stable Wnt5A overexpressing clones. The expression levels of Frizzled (FZD)-2 and -5, were increased in different clones. However ROR-1, -2 expression levels were differently regulated in clones. Wnt5A overexpressing clones showed increased cell proliferation, migration, and clonogenicity. Moreover, Wnt5A overexpressing SKOV-3 clone showed increased MCAs formation ability. Cell invasion had been increased in OVCAR-3-derived clones, while this was decreased in SKOV-3-derived clone. Importantly, αv integrin expression levels were increased in all assessed clones, accompanied by increased cell attachment to fibronectin and focal adhesion kinase activity. Moreover, the treatment of clones with Box5 as a Wnt5A/FZD5 antagonist abrogates ITGAV increase, cell proliferation, migration, and their attachment to fibronectin. Accordingly, we observed significantly higher expression levels of ITGAV and ITGB3 in human high-grade serous ovarian cancer specimens and ITGAV correlated positively with Wnt5A in metastatic serous type ovarian cancer. In summary, we hypothesize here, that Wnt5A/FZD-5 signaling modulate αv integrin expression levels that could be associated with ovarian cancer cell proliferation, migration, and fibronectin attachment.
format article
author Vajihe Azimian-Zavareh
Zeinab Dehghani-Ghobadi
Marzieh Ebrahimi
Kian Mirzazadeh
Irina Nazarenko
Ghamartaj Hossein
author_facet Vajihe Azimian-Zavareh
Zeinab Dehghani-Ghobadi
Marzieh Ebrahimi
Kian Mirzazadeh
Irina Nazarenko
Ghamartaj Hossein
author_sort Vajihe Azimian-Zavareh
title Wnt5A modulates integrin expression in a receptor-dependent manner in ovarian cancer cells
title_short Wnt5A modulates integrin expression in a receptor-dependent manner in ovarian cancer cells
title_full Wnt5A modulates integrin expression in a receptor-dependent manner in ovarian cancer cells
title_fullStr Wnt5A modulates integrin expression in a receptor-dependent manner in ovarian cancer cells
title_full_unstemmed Wnt5A modulates integrin expression in a receptor-dependent manner in ovarian cancer cells
title_sort wnt5a modulates integrin expression in a receptor-dependent manner in ovarian cancer cells
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/b7767adc982e415e8a35af79b5a07103
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