YAP drives cutaneous squamous cell carcinoma formation and progression
YAP drives cutaneous squamous cell carcinoma formation and progression
Squamous cell carcinoma (SCC) can progress to malignant metastatic cancer, including an aggressive subtype known as spindle cell carcinoma (spSCC). spSCC formation involves epithelial-to-mesenchymal transition (EMT), yet the molecular basis of this event remains unknown. The transcriptional co-activator YAP undergoes recurrent amplification in human SCC and overexpression of YAP drives SCC formation in mice. Here, we show that human spSCC tumours also feature strong nuclear localisation of YAP and overexpression of activated YAP (NLS-YAP-5SA) with Keratin-5 (K5-CreERt) is sufficient to induce rapid formation of both SCC and spSCC in mice. spSCC tumours arise at sites of epithelial scratch wounding, where tumour-initiating epithelial cells undergo EMT to generate spSCC. Expression of the EMT transcription factor ZEB1 arises upon wounding and is a defining characteristic of spSCC in mice and humans. Thus, the wound healing response synergises with YAP to drive metaplastic transformation of SCC to spSCC.
Vincent-Mistiaen, Zoé
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Elbediwy, Ahmed
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Vanyai, Hannah
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Cotton, Jennifer
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Stamp, Gordon
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Nye, Emma
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Spencer-Dene, Bradley
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Thomas, Gareth J.
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Mao, Junhao
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Thompson, Barry
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September 2018
Vincent-Mistiaen, Zoé
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Elbediwy, Ahmed
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Vanyai, Hannah
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Cotton, Jennifer
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Stamp, Gordon
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Nye, Emma
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Spencer-Dene, Bradley
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Thomas, Gareth J.
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Mao, Junhao
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Thompson, Barry
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Vincent-Mistiaen, Zoé, Elbediwy, Ahmed, Vanyai, Hannah, Cotton, Jennifer, Stamp, Gordon, Nye, Emma, Spencer-Dene, Bradley, Thomas, Gareth J., Mao, Junhao and Thompson, Barry
(2018)
YAP drives cutaneous squamous cell carcinoma formation and progression.
eLife, 7, [e33304].
(doi:10.7554/eLife.33304).
Abstract
Squamous cell carcinoma (SCC) can progress to malignant metastatic cancer, including an aggressive subtype known as spindle cell carcinoma (spSCC). spSCC formation involves epithelial-to-mesenchymal transition (EMT), yet the molecular basis of this event remains unknown. The transcriptional co-activator YAP undergoes recurrent amplification in human SCC and overexpression of YAP drives SCC formation in mice. Here, we show that human spSCC tumours also feature strong nuclear localisation of YAP and overexpression of activated YAP (NLS-YAP-5SA) with Keratin-5 (K5-CreERt) is sufficient to induce rapid formation of both SCC and spSCC in mice. spSCC tumours arise at sites of epithelial scratch wounding, where tumour-initiating epithelial cells undergo EMT to generate spSCC. Expression of the EMT transcription factor ZEB1 arises upon wounding and is a defining characteristic of spSCC in mice and humans. Thus, the wound healing response synergises with YAP to drive metaplastic transformation of SCC to spSCC.
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elife-33304-v1
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Accepted/In Press date: 29 June 2018
e-pub ahead of print date: 20 September 2018
Published date: September 2018
Identifiers
Local EPrints ID: 427265
URI: http://eprints.soton.ac.uk/id/eprint/427265
ISSN: 2050-084X
PURE UUID: 7bb6e854-7e48-4c81-89af-f0a7bcc875b0
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Date deposited: 10 Jan 2019 17:30
Last modified: 05 Jun 2024 19:29
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Contributors
Author:
Zoé Vincent-Mistiaen
Author:
Ahmed Elbediwy
Author:
Hannah Vanyai
Author:
Jennifer Cotton
Author:
Gordon Stamp
Author:
Emma Nye
Author:
Bradley Spencer-Dene
Author:
Junhao Mao
Author:
Barry Thompson
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