期刊
MOLECULAR CANCER RESEARCH
卷 13, 期 6, 页码 957-968出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-14-0580
关键词
-
资金
- Oral Cancer Affinity Research Collaborative group at Boston University
- Boston University Oral Cancer Research Initiative (OCRI)
- CTSI [U54-TR001012]
- March of Dimes Foundation [1-FY14-219]
- CDMRP [W81XWH-14-1-0336]
- NIH National Heart Lung and Blood Institute [1R01HL124392-01]
- NIH-National Institute of Dental and Craniofacial Research [DE RO1 014437]
- Massachusetts Green High-Performance Computing Center grant
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 death rates associated with the disease are particularly high. Despite progress in understanding 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 (YAP1) and TAZ (WWTR1), which are key effectors of the Hippo pathway, drive protumorigenic signals in OSCC. Regions of premalignant oral tissues exhibit aberrant nuclear YAP accumulation, suggesting that dysregulated YAP activity contributes to the onset of OSCC. Supporting this premise, we determined 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. Global gene expression profiles associated with YAP and TAZ knockdown revealed changes in the control of gene expression implicated in protumorigenic signaling, including those 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. (C) 2015 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据