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Integrative genomic and functional analysis of human oral squamous cell carcinoma cell lines reveals synergistic effects of FAT1 and CASP8 inactivation

Research output: Contribution to journalArticle

Tyler F. Hayes, Nathan Benaich, Stephen J. Goldie, Kalle Sipilä, Ashley Ames-Draycott, Wenjun Cai, Guangliang Yin, Fiona M. Watt

Original languageEnglish
Pages (from-to)106-114
Number of pages9
JournalCancer Letters
Volume383
Issue number1
Early online date28 Sep 2016
DOIs
Accepted/In press8 Sep 2016
E-pub ahead of print28 Sep 2016
Published1 Dec 2016

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Abstract

Oral squamous cell carcinoma (OSCC) is genetically highly heterogeneous, which contributes to the challenges of treatment. To create an in vitro model that accurately reflects this heterogeneity, we generated a panel of HPV-negative OSCC cell lines. By whole exome sequencing of the lines and matched patient blood samples, we demonstrate that the mutational spectrum of the lines is representative of primary OSCC in The Cancer Genome Atlas. We show that loss of function mutations in FAT1 (an atypical cadherin) and CASP8 (Caspase 8) frequently occur in the same tumour. OSCC cells with inactivating FAT1 mutations exhibited reduced intercellular adhesion. Knockdown of FAT1 and CASP8 individually or in combination in OSCC cells led to increased cell migration and clonal growth, resistance to Staurosporine-induced apoptosis and, in some cases, increased terminal differentiation. The OSCC lines thus represent a valuable resource for elucidating the impact of different mutations on tumour behaviour.

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