FOXA1, GATA3 and PPARɣ Cooperate to Drive Luminal Subtype in Bladder Cancer: A Molecular Analysis of Established Human Cell Lines.
FOXA1, GATA3 and PPARɣ Cooperate to Drive Luminal Subtype in Bladder Cancer: A Molecular Analysis of Established Human Cell Lines.
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DOI：
10.1038/srep38531
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发表时间：
2016-12-07
影响因子：
4.6
通讯作者：
DeGraff DJ
中科院分区：
文献类型：
--
作者：
Warrick JI;Walter V;Yamashita H;Chung E;Shuman L;Amponsa VO;Zheng Z;Chan W;Whitcomb TL;Yue F;Iyyanki T;Kawasawa YI;Kaag M;Guo W;Raman JD;Park JS;DeGraff DJ
离散的膀胱癌分子亚型表现出不同的临床侵袭性和治疗反应，这可能对确定这种常见恶性肿瘤的新治疗方法具有重要意义。然而，由于缺乏合适的模型来研究每个亚型，研究受到阻碍。为了解决这一限制，我们使用癌细胞系百科全书（CCLE）中的药理学可用数据，通过癌症基因组图谱（TCGA）对膀胱癌的基因组表征指导，将膀胱癌细胞系分类为分子亚型。这鉴定了一组膀胱癌细胞系，其表现出与人类疾病的管腔和基底分子亚型一致的遗传改变和基因表达模式。膀胱癌细胞系的一个子集表现出与管腔和基底亚型一致的体内组织形态学模式，包括乳头状结构和鳞状分化。使用分子亚型分配和我们自己的RNA-seq分析，我们发现GATA 3和FOXA 1的过表达与PPAR γ活化协同作用，以驱动基底膀胱癌细胞转分化为Luminial表型。总之，我们的分析确定了一组适用于膀胱癌分子亚型研究的人细胞系，并进一步表明了由GATA 3、FOXA 1和PPAR γ组成的协同调控网络驱动管腔细胞命运。
Discrete bladder cancer molecular subtypes exhibit differential clinical aggressiveness and therapeutic response, which may have significant implications for identifying novel treatments for this common malignancy. However, research is hindered by the lack of suitable models to study each subtype. To address this limitation, we classified bladder cancer cell lines into molecular subtypes using publically available data in the Cancer Cell Line Encyclopedia (CCLE), guided by genomic characterization of bladder cancer by The Cancer Genome Atlas (TCGA). This identified a panel of bladder cancer cell lines which exhibit genetic alterations and gene expression patterns consistent with luminal and basal molecular subtypes of human disease. A subset of bladder cancer cell lines exhibit in vivo histomorphologic patterns consistent with luminal and basal subtypes, including papillary architecture and squamous differentiation. Using the molecular subtype assignments, and our own RNA-seq analysis, we found overexpression of GATA3 and FOXA1 cooperate with PPARɣ activation to drive transdifferentiation of a basal bladder cancer cells to a luminial phenotype. In summary, our analysis identified a set of human cell lines suitable for the study of molecular subtypes in bladder cancer, and furthermore indicates a cooperative regulatory network consisting of GATA3, FOXA1, and PPARɣ drive luminal cell fate.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
--
作者：
Drayton RM;Peter S;Myers K;Miah S;Dudziec E;Bryant HE;Catto JW
通讯作者：
Catto JW
影响因子：
5.8
作者：
Dabney, AR
通讯作者：
Dabney, AR
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
11.2
作者：
He F;Melamed J;Tang MS;Huang C;Wu XR
通讯作者：
Wu XR