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Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling

The epithelial-mesenchymal transition (EMT) endows carcinoma cells with traits needed to complete many of the steps leading to metastasis formation, but its contributions specifically to the late step of extravasation remain understudied. We find that breast cancer cells that have undergone an EMT e...

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Autores principales: Fröse, Julia, Chen, Michelle B., Hebron, Katie E., Reinhardt, Ferenc, Hajal, Cynthia, Zijlstra, Andries, Kamm, Roger D., Weinberg, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181240/
https://www.ncbi.nlm.nih.gov/pubmed/30044991
http://dx.doi.org/10.1016/j.celrep.2018.06.092
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author Fröse, Julia
Chen, Michelle B.
Hebron, Katie E.
Reinhardt, Ferenc
Hajal, Cynthia
Zijlstra, Andries
Kamm, Roger D.
Weinberg, Robert A.
author_facet Fröse, Julia
Chen, Michelle B.
Hebron, Katie E.
Reinhardt, Ferenc
Hajal, Cynthia
Zijlstra, Andries
Kamm, Roger D.
Weinberg, Robert A.
author_sort Fröse, Julia
collection PubMed
description The epithelial-mesenchymal transition (EMT) endows carcinoma cells with traits needed to complete many of the steps leading to metastasis formation, but its contributions specifically to the late step of extravasation remain understudied. We find that breast cancer cells that have undergone an EMT extravasate more efficiently from blood vessels both in vitro and in vivo. Analysis of gene expression changes associated with the EMT program led to the identification of an EMTinduced cell-surface protein, podocalyxin (PODXL), as a key mediator of extravasation in mesenchymal breast and pancreatic carcinoma cells. PODXL promotes extravasation through direct interaction of its intracellular domain with the cytoskeletal linker protein ezrin. Ezrin proceeds to establish dorsal cortical polarity, enabling the transition of cancer cells from a non-polarized, rounded cell morphology to an invasive extravasation-competent shape. Hence, the EMT program can directly enhance the efficiency of extravasation and subsequent metastasis formation through a PODXL-ezrin signaling axis.
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spelling pubmed-61812402018-10-11 Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling Fröse, Julia Chen, Michelle B. Hebron, Katie E. Reinhardt, Ferenc Hajal, Cynthia Zijlstra, Andries Kamm, Roger D. Weinberg, Robert A. Cell Rep Article The epithelial-mesenchymal transition (EMT) endows carcinoma cells with traits needed to complete many of the steps leading to metastasis formation, but its contributions specifically to the late step of extravasation remain understudied. We find that breast cancer cells that have undergone an EMT extravasate more efficiently from blood vessels both in vitro and in vivo. Analysis of gene expression changes associated with the EMT program led to the identification of an EMTinduced cell-surface protein, podocalyxin (PODXL), as a key mediator of extravasation in mesenchymal breast and pancreatic carcinoma cells. PODXL promotes extravasation through direct interaction of its intracellular domain with the cytoskeletal linker protein ezrin. Ezrin proceeds to establish dorsal cortical polarity, enabling the transition of cancer cells from a non-polarized, rounded cell morphology to an invasive extravasation-competent shape. Hence, the EMT program can directly enhance the efficiency of extravasation and subsequent metastasis formation through a PODXL-ezrin signaling axis. 2018-07-24 /pmc/articles/PMC6181240/ /pubmed/30044991 http://dx.doi.org/10.1016/j.celrep.2018.06.092 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Fröse, Julia
Chen, Michelle B.
Hebron, Katie E.
Reinhardt, Ferenc
Hajal, Cynthia
Zijlstra, Andries
Kamm, Roger D.
Weinberg, Robert A.
Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling
title Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling
title_full Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling
title_fullStr Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling
title_full_unstemmed Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling
title_short Epithelial-Mesenchymal Transition Induces Podocalyxin to Promote Extravasation via Ezrin Signaling
title_sort epithelial-mesenchymal transition induces podocalyxin to promote extravasation via ezrin signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181240/
https://www.ncbi.nlm.nih.gov/pubmed/30044991
http://dx.doi.org/10.1016/j.celrep.2018.06.092
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