The RhoA dependent anti-metastatic function of RKIP in breast cancer

Abstract Raf-1 kinase inhibitor protein was initially discovered as a physiological kinase inhibitor of the MAPK signaling pathway and was later shown to suppress cancer cell invasion and metastasis. Yet, the molecular mechanism through which RKIP executes its effects is not completely defined. RhoA...

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Autores principales:	Gardiyawasam Kalpana, Christopher Figy, Jingwei Feng, Claire Tipton, Julius N. De Castro, Vu N. Bach, Clariza Borile, Alexandria LaSalla, Hussain N. Odeh, Miranda Yeung, Rafael Garcia-Mata, Kam C. Yeung
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b66068fddf0e4d31bf3c96e3e386a80c
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spelling	oai:doaj.org-article:b66068fddf0e4d31bf3c96e3e386a80c2021-12-02T17:51:12ZThe RhoA dependent anti-metastatic function of RKIP in breast cancer10.1038/s41598-021-96709-62045-2322https://doaj.org/article/b66068fddf0e4d31bf3c96e3e386a80c2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96709-6https://doaj.org/toc/2045-2322Abstract Raf-1 kinase inhibitor protein was initially discovered as a physiological kinase inhibitor of the MAPK signaling pathway and was later shown to suppress cancer cell invasion and metastasis. Yet, the molecular mechanism through which RKIP executes its effects is not completely defined. RhoA has both a pro- and anti-metastatic cell-context dependent functions. Given that Rho GTPases primarily function on actin cytoskeleton dynamics and cell movement regulation, it is possible that one way RKIP hinders cancer cell invasion/metastasis is by targeting these proteins. Here we show that RKIP inhibits cancer cell invasion and metastasis by stimulating RhoA anti-tumorigenic functions. Mechanistically, RKIP activates RhoA in an Erk2 and GEF-H1 dependent manner to enhance E-cadherin membrane localization and inhibit CCL5 expression.Gardiyawasam KalpanaChristopher FigyJingwei FengClaire TiptonJulius N. De CastroVu N. BachClariza BorileAlexandria LaSallaHussain N. OdehMiranda YeungRafael Garcia-MataKam C. YeungNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gardiyawasam Kalpana Christopher Figy Jingwei Feng Claire Tipton Julius N. De Castro Vu N. Bach Clariza Borile Alexandria LaSalla Hussain N. Odeh Miranda Yeung Rafael Garcia-Mata Kam C. Yeung The RhoA dependent anti-metastatic function of RKIP in breast cancer
description	Abstract Raf-1 kinase inhibitor protein was initially discovered as a physiological kinase inhibitor of the MAPK signaling pathway and was later shown to suppress cancer cell invasion and metastasis. Yet, the molecular mechanism through which RKIP executes its effects is not completely defined. RhoA has both a pro- and anti-metastatic cell-context dependent functions. Given that Rho GTPases primarily function on actin cytoskeleton dynamics and cell movement regulation, it is possible that one way RKIP hinders cancer cell invasion/metastasis is by targeting these proteins. Here we show that RKIP inhibits cancer cell invasion and metastasis by stimulating RhoA anti-tumorigenic functions. Mechanistically, RKIP activates RhoA in an Erk2 and GEF-H1 dependent manner to enhance E-cadherin membrane localization and inhibit CCL5 expression.
format	article
author	Gardiyawasam Kalpana Christopher Figy Jingwei Feng Claire Tipton Julius N. De Castro Vu N. Bach Clariza Borile Alexandria LaSalla Hussain N. Odeh Miranda Yeung Rafael Garcia-Mata Kam C. Yeung
author_facet	Gardiyawasam Kalpana Christopher Figy Jingwei Feng Claire Tipton Julius N. De Castro Vu N. Bach Clariza Borile Alexandria LaSalla Hussain N. Odeh Miranda Yeung Rafael Garcia-Mata Kam C. Yeung
author_sort	Gardiyawasam Kalpana
title	The RhoA dependent anti-metastatic function of RKIP in breast cancer
title_short	The RhoA dependent anti-metastatic function of RKIP in breast cancer
title_full	The RhoA dependent anti-metastatic function of RKIP in breast cancer
title_fullStr	The RhoA dependent anti-metastatic function of RKIP in breast cancer
title_full_unstemmed	The RhoA dependent anti-metastatic function of RKIP in breast cancer
title_sort	rhoa dependent anti-metastatic function of rkip in breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b66068fddf0e4d31bf3c96e3e386a80c
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The RhoA dependent anti-metastatic function of RKIP in breast cancer

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