Department of Molecular, Cell and Cancer Biology
Cancer Biology | Cell Biology | Developmental Biology | Neoplasms
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.
Hippo pathway, YAP, carcinoma, developmental biology, mouse, regenerative medicine, stem cells
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Copyright © 2018, Vincent-Mistiaen et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
DOI of Published Version
Elife. 2018 Sep 20;7. pii: 33304. doi: 10.7554/eLife.33304. Link to article on publisher's site
Vincent-Mistiaen, Zoe; Elbediwy, Ahmed; Vanyai, Hannah; Cotton, Jennifer L.; Stamp, Gordon; Nye, Emma; Spencer-Dene, Bradley; Thomas, Gareth J.; Mao, Junhao; and Thompson, Barry, "YAP drives cutaneous squamous cell carcinoma formation and progression" (2018). Open Access Articles. 3620.
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This work is licensed under a Creative Commons Attribution 4.0 License.