生物
头颈部鳞状细胞癌
表皮生长因子受体
癌症研究
卵泡抑素
转化生长因子
肿瘤微环境
转录因子
转录组
表型
肿瘤进展
癌症
细胞生物学
基因表达
基因
遗传学
头颈部癌
肿瘤细胞
作者
Akinsola Oyelakin,Jennifer Sosa,Kasturi Bala Nayak,Alexandra Glathar,Christian Gluck,Isha Sethi,Maria Tsompana,Norma J. Nowak,Michael Buck,Rose‐Anne Romano,Satrajit Sinha
出处
期刊:NAR cancer
[Oxford University Press]
日期:2023-06-09
卷期号:5 (3)
被引量:3
标识
DOI:10.1093/narcan/zcad038
摘要
Abstract Although numerous putative oncogenes have been associated with the etiology of head and neck squamous cell carcinoma (HNSCC), the mechanisms by which these oncogenes and their downstream targets mediate tumor progression have not been fully elucidated. We performed an integrative analysis to identify a crucial set of targets of the oncogenic transcription factor p63 that are common across multiple transcriptomic datasets obtained from HNSCC patients, and representative cell line models. Notably, our analysis revealed FST which encodes follistatin, a secreted glycoprotein that inhibits the transforming growth factor TGFβ/activin signaling pathways, to be a direct transcriptional target of p63. In addition, we found that FST expression is also driven by epidermal growth factor receptor EGFR signaling, thus mediating a functional link between the TGF-β and EGFR pathways. We show through loss- and gain-of-function studies that FST predominantly imparts a tumor-growth and migratory phenotype in HNSCC cells. Furthermore, analysis of single-cell RNA sequencing data from HNSCC patients unveiled cancer cells as the dominant source of FST within the tumor microenvironment and exposed a correlation between the expression of FST and its regulators with immune infiltrates. We propose FST as a prognostic biomarker for patient survival and a compelling candidate mediating the broad effects of p63 on the tumor and its associated microenvironment.
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