Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells
In a tumor microenvironment, endothelial cell migration and angiogenesis allow cancer to spread to other organs causing metastasis. Indeed, a number of molecules that are involved in cytoskeleton re-organization and intracellular signaling have been investigated for their effects on tumor cell grow...
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Online Access: | http://dx.doi.org/10.1080/19336918.2018.1516982 |
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doaj-35401d0a63a6462bbc1acd054738cfdb2021-01-04T18:02:33ZengTaylor & Francis GroupCell Adhesion & Migration1933-69181933-69262020-01-0114112913810.1080/19336918.2018.15169821516982Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cellsMariana Costa Braga Schmidt0Katia L.P. Morais1Maíra Estanislau Soares de Almeida2Asif Iqbal3Mauricio Barbugiani Goldfeder4Ana Marisa Chudzinski-Tavassi5Butantan InstituteButantan InstituteButantan InstituteButantan InstituteButantan InstituteButantan InstituteIn a tumor microenvironment, endothelial cell migration and angiogenesis allow cancer to spread to other organs causing metastasis. Indeed, a number of molecules that are involved in cytoskeleton re-organization and intracellular signaling have been investigated for their effects on tumor cell growth and metastasis. Alongside that, Amblyomin-X, a recombinant Kunitz-type protein, has been shown to reduce metastasis and tumor growth in in vivo experiments. In the present report, we provide a mechanistic insight to these antitumor effects, this is, Amblyomin-X modulates Rho-GTPases and uPAR signaling, and reduces the release of MMPs, leading to disruption of the actin cytoskeleton and decreased cell migration of tumor cell lines. Altogether, our data support a role for Amblyomin-X as a novel potential antitumor drug. Abbreviations Amb-X: Amblyomin-X; ECGF: endotelial cell growth factor; ECM: extracellular matrix; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HUVEC: human umbilical vein endothelial cell; LRP1: low-density lipoprotein receptor-related protein; MMP: matrix metalloproteinase; HPI-4: hedgehog pathway inhibitor 4; PAI-1: plasminogen activator inhibitor 1; PMA: phorbol 12-myristate-13-acetate; TFPI: tissue factor pathway inhibitor; uPA: urokinase plasminogen activator; uPAR: uPA receptor.http://dx.doi.org/10.1080/19336918.2018.1516982amblyomin-xkunitz-type inhibitorcytoskeletonmigrationuparrho-gtpase |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mariana Costa Braga Schmidt Katia L.P. Morais Maíra Estanislau Soares de Almeida Asif Iqbal Mauricio Barbugiani Goldfeder Ana Marisa Chudzinski-Tavassi |
spellingShingle |
Mariana Costa Braga Schmidt Katia L.P. Morais Maíra Estanislau Soares de Almeida Asif Iqbal Mauricio Barbugiani Goldfeder Ana Marisa Chudzinski-Tavassi Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells Cell Adhesion & Migration amblyomin-x kunitz-type inhibitor cytoskeleton migration upar rho-gtpase |
author_facet |
Mariana Costa Braga Schmidt Katia L.P. Morais Maíra Estanislau Soares de Almeida Asif Iqbal Mauricio Barbugiani Goldfeder Ana Marisa Chudzinski-Tavassi |
author_sort |
Mariana Costa Braga Schmidt |
title |
Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells |
title_short |
Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells |
title_full |
Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells |
title_fullStr |
Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells |
title_full_unstemmed |
Amblyomin-X, a recombinant Kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells |
title_sort |
amblyomin-x, a recombinant kunitz-type inhibitor, regulates cell adhesion and migration of human tumor cells |
publisher |
Taylor & Francis Group |
series |
Cell Adhesion & Migration |
issn |
1933-6918 1933-6926 |
publishDate |
2020-01-01 |
description |
In a tumor microenvironment, endothelial cell migration and angiogenesis allow cancer to spread to other organs causing metastasis. Indeed, a number of molecules that are involved in cytoskeleton re-organization and intracellular signaling have been investigated for their effects on tumor cell growth and metastasis. Alongside that, Amblyomin-X, a recombinant Kunitz-type protein, has been shown to reduce metastasis and tumor growth in in vivo experiments. In the present report, we provide a mechanistic insight to these antitumor effects, this is, Amblyomin-X modulates Rho-GTPases and uPAR signaling, and reduces the release of MMPs, leading to disruption of the actin cytoskeleton and decreased cell migration of tumor cell lines. Altogether, our data support a role for Amblyomin-X as a novel potential antitumor drug. Abbreviations Amb-X: Amblyomin-X; ECGF: endotelial cell growth factor; ECM: extracellular matrix; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HUVEC: human umbilical vein endothelial cell; LRP1: low-density lipoprotein receptor-related protein; MMP: matrix metalloproteinase; HPI-4: hedgehog pathway inhibitor 4; PAI-1: plasminogen activator inhibitor 1; PMA: phorbol 12-myristate-13-acetate; TFPI: tissue factor pathway inhibitor; uPA: urokinase plasminogen activator; uPAR: uPA receptor. |
topic |
amblyomin-x kunitz-type inhibitor cytoskeleton migration upar rho-gtpase |
url |
http://dx.doi.org/10.1080/19336918.2018.1516982 |
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