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A YAP/TAZ‐Regulated Transcriptional Signature Associated with Oral Squamous Cell Carcinoma
Author(s) -
Hiemer Samantha,
Zhang Liye,
Kartha Vinay,
Packer Trevor,
Almershed Munirah,
Noonan Viki,
Kukuruzinska Maria,
Bais Manish,
Monti Stefano,
Varelas Xaralabos
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb124
Subject(s) - hippo signaling pathway , biology , cancer research , gene knockdown , metastasis , cancer , carcinogenesis , gene signature , cell growth , tumor progression , gene , gene expression , genetics
Oral squamous cell carcinoma (OSCC) is a prevalent form of cancer that develops from the epithelium of the oral cavity. OSCC is on the rise worldwide, and the death rates associated with the disease are particularly high. Despite progress in the understanding of the mutational and expression landscape associated with OSCC, advances in deciphering these alterations for the development of therapeutic strategies have been limited. Further insight into the molecular cues that contribute to OSCC is therefore required. Here we show that the transcriptional regulators YAP and TAZ, which are key effectors of the Hippo pathway, drive pro‐tumorigenic signals in OSCC. Regions of pre‐malignant oral tissues exhibit aberrant nuclear YAP accumulation, suggesting that dysregulated YAP activity contributes to the onset of OSCC. Supporting this premise, we found that nuclear YAP and TAZ activity drives OSCC cell proliferation, survival, and migration in vitro, and is required for OSCC tumor growth and metastasis in vivo. Analyses of the global gene expression changes associated with YAP and TAZ knockdown revealed roles in the control of genes important for pro‐tumorigenic signaling, including those encoding factors required for cell cycle progression and survival. Notably, the transcriptional signature regulated by YAP and TAZ significantly correlates with gene expression changes occurring in human OSCCs identified by “The Cancer Genome Atlas” (TCGA), emphasizing a central role for YAP and TAZ in OSCC biology. This study defines a YAP/TAZ‐regulated transcriptional program in OSCC, and reveals novel roles for nuclear YAP/TAZ activity in the onset and progression of this cancer.