Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Gardberg, Maria, Kaipio, Katja, Lehtinen, Laura, Mikkonen, Piia, Heuser, Vanina D., Talvinen, Kati, Iljin, Kristiina, Kampf, Caroline, Uhlen, Mathias, Grénman, Reidar, Koivisto, Mari, Carpén, Olli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784416/
https://www.ncbi.nlm.nih.gov/pubmed/24086398
http://dx.doi.org/10.1371/journal.pone.0074923
_version_ 1782477556364083200
author Gardberg, Maria
Kaipio, Katja
Lehtinen, Laura
Mikkonen, Piia
Heuser, Vanina D.
Talvinen, Kati
Iljin, Kristiina
Kampf, Caroline
Uhlen, Mathias
Grénman, Reidar
Koivisto, Mari
Carpén, Olli
author_facet Gardberg, Maria
Kaipio, Katja
Lehtinen, Laura
Mikkonen, Piia
Heuser, Vanina D.
Talvinen, Kati
Iljin, Kristiina
Kampf, Caroline
Uhlen, Mathias
Grénman, Reidar
Koivisto, Mari
Carpén, Olli
author_sort Gardberg, Maria
collection PubMed
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 Online
Article
Text
id pubmed-3784416
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-37844162013-10-01 FHOD1, a Formin Upregulated in Epithelial-Mesenchymal Transition, Participates in Cancer Cell Migration and Invasion Gardberg, Maria Kaipio, Katja Lehtinen, Laura Mikkonen, Piia Heuser, Vanina D. Talvinen, Kati Iljin, Kristiina Kampf, Caroline Uhlen, Mathias Grénman, Reidar Koivisto, Mari Carpén, Olli PLoS One Research Article 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. Public Library of Science 2013-09-26 /pmc/articles/PMC3784416/ /pubmed/24086398 http://dx.doi.org/10.1371/journal.pone.0074923 Text en © 2013 Gardberg et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gardberg, Maria
Kaipio, Katja
Lehtinen, Laura
Mikkonen, Piia
Heuser, Vanina D.
Talvinen, Kati
Iljin, Kristiina
Kampf, Caroline
Uhlen, Mathias
Grénman, Reidar
Koivisto, Mari
Carpén, Olli
FHOD1, a Formin Upregulated in Epithelial-Mesenchymal Transition, Participates in Cancer Cell Migration and Invasion
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784416/
https://www.ncbi.nlm.nih.gov/pubmed/24086398
http://dx.doi.org/10.1371/journal.pone.0074923
work_keys_str_mv AT gardbergmaria fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion
AT kaipiokatja fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion
AT lehtinenlaura fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion
AT mikkonenpiia fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion
AT heuservaninad fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion
AT talvinenkati fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion
AT iljinkristiina fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion
AT kampfcaroline fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion
AT uhlenmathias fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion
AT grenmanreidar fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion
AT koivistomari fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion
AT carpenolli fhod1aforminupregulatedinepithelialmesenchymaltransitionparticipatesincancercellmigrationandinvasion