FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.

Cancer cells can obtain their ability to invade and metastasise by undergoing epithelial-to-mesenchymal transition (EMT). Exploiting this mechanism of cellular plasticity, malignant cells can remodel their actin cytoskeleton and down-regulate proteins needed for cell-cell contacts. The mechanisms of...

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Autores principales:	Maria Gardberg, Katja Kaipio, Laura Lehtinen, Piia Mikkonen, Vanina D Heuser, Kati Talvinen, Kristiina Iljin, Caroline Kampf, Mathias Uhlen, Reidar Grénman, Mari Koivisto, Olli Carpén
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9a9e4393398648228343bb90688dd4d8
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spelling	oai:doaj.org-article:9a9e4393398648228343bb90688dd4d82021-11-18T08:53:35ZFHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.1932-620310.1371/journal.pone.0074923https://doaj.org/article/9a9e4393398648228343bb90688dd4d82013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086398/?tool=EBIhttps://doaj.org/toc/1932-6203Cancer cells can obtain their ability to invade and metastasise by undergoing epithelial-to-mesenchymal transition (EMT). Exploiting this mechanism of cellular plasticity, malignant cells can remodel their actin cytoskeleton and down-regulate proteins needed for cell-cell contacts. The mechanisms of cytoskeletal reorganisation resulting in mesenchymal morphology and increased invasive potential are poorly understood. Actin nucleating formins have been implicated as key players in EMT. Here, we analysed which formins are altered in squamous cell carcinoma related EMT. FHOD1, a poorly studied formin, appeared to be markedly upregulated upon EMT. In human tissues FHOD1 was primarily expressed in mesenchymal cells, with little expression in epithelia. However, specimens from oral squamous cell cancers demonstrated consistent FHOD1 upregulation in mesenchymally transformed cells at the invasive edge. This upregulation was confirmed in an oral squamous carcinoma model, where FHOD1 expression was markedly increased upon EMT in a PI3K signalling dependent manner. In the EMT cells FHOD1 contributed to the spindle-shaped morphology and mesenchymal F-actin organization. Furthermore, functional assays demonstrated that FHOD1 contributes to cell migration and invasion. Finally, FHOD1 depletion reduced the ability of EMT cancer cells to form invadopodia and to degrade extracellular matrix. Our results indicate that FHOD1 participates in cytoskeletal changes in EMT. In addition, we show that FHOD1 upregulation occurs during cancer cell EMT in vivo, which indicates that FHOD1 may contribute to tumour progression.Maria GardbergKatja KaipioLaura LehtinenPiia MikkonenVanina D HeuserKati TalvinenKristiina IljinCaroline KampfMathias UhlenReidar GrénmanMari KoivistoOlli CarpénPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e74923 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria Gardberg Katja Kaipio Laura Lehtinen Piia Mikkonen Vanina D Heuser Kati Talvinen Kristiina Iljin Caroline Kampf Mathias Uhlen Reidar Grénman Mari Koivisto Olli Carpén FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.
description	Cancer cells can obtain their ability to invade and metastasise by undergoing epithelial-to-mesenchymal transition (EMT). Exploiting this mechanism of cellular plasticity, malignant cells can remodel their actin cytoskeleton and down-regulate proteins needed for cell-cell contacts. The mechanisms of cytoskeletal reorganisation resulting in mesenchymal morphology and increased invasive potential are poorly understood. Actin nucleating formins have been implicated as key players in EMT. Here, we analysed which formins are altered in squamous cell carcinoma related EMT. FHOD1, a poorly studied formin, appeared to be markedly upregulated upon EMT. In human tissues FHOD1 was primarily expressed in mesenchymal cells, with little expression in epithelia. However, specimens from oral squamous cell cancers demonstrated consistent FHOD1 upregulation in mesenchymally transformed cells at the invasive edge. This upregulation was confirmed in an oral squamous carcinoma model, where FHOD1 expression was markedly increased upon EMT in a PI3K signalling dependent manner. In the EMT cells FHOD1 contributed to the spindle-shaped morphology and mesenchymal F-actin organization. Furthermore, functional assays demonstrated that FHOD1 contributes to cell migration and invasion. Finally, FHOD1 depletion reduced the ability of EMT cancer cells to form invadopodia and to degrade extracellular matrix. Our results indicate that FHOD1 participates in cytoskeletal changes in EMT. In addition, we show that FHOD1 upregulation occurs during cancer cell EMT in vivo, which indicates that FHOD1 may contribute to tumour progression.
format	article
author	Maria Gardberg Katja Kaipio Laura Lehtinen Piia Mikkonen Vanina D Heuser Kati Talvinen Kristiina Iljin Caroline Kampf Mathias Uhlen Reidar Grénman Mari Koivisto Olli Carpén
author_facet	Maria Gardberg Katja Kaipio Laura Lehtinen Piia Mikkonen Vanina D Heuser Kati Talvinen Kristiina Iljin Caroline Kampf Mathias Uhlen Reidar Grénman Mari Koivisto Olli Carpén
author_sort	Maria Gardberg
title	FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.
title_short	FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.
title_full	FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.
title_fullStr	FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.
title_full_unstemmed	FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.
title_sort	fhod1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9a9e4393398648228343bb90688dd4d8
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FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in cancer cell migration and invasion.

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