FOXA1, GATA3 and PPARIγ Cooperate to drive luminal subtype in bladder cancer: A molecular analysis of established human cell lines

Joshua Warrick, Vonn Walter, Hironobu Yamashita, Eunah Chung, Lauren Shuman, Vasty Osei Amponsa, Zongyu Zheng, Wilson Chan, Tiffany Whitcomb, Feng Yue, Tejaswi Iyyanki, Yuka Imamura, Matthew G. Kaag, Wansong Guo, Jay Raman, Joo Seop Park, David Degraff

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 PPARI 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 PPARI drive luminal cell fate.

Original languageEnglish (US)
Article number38531
JournalScientific reports
Volume6
DOIs
StatePublished - Dec 7 2016

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Urinary Bladder Neoplasms
Cell Line
Basal Cell Neoplasms
Encyclopedias
Neoplasms
Atlases
Genome
RNA
Phenotype
Gene Expression
Research

All Science Journal Classification (ASJC) codes

  • General

Cite this

Warrick, Joshua ; Walter, Vonn ; Yamashita, Hironobu ; Chung, Eunah ; Shuman, Lauren ; Amponsa, Vasty Osei ; Zheng, Zongyu ; Chan, Wilson ; Whitcomb, Tiffany ; Yue, Feng ; Iyyanki, Tejaswi ; Imamura, Yuka ; Kaag, Matthew G. ; Guo, Wansong ; Raman, Jay ; Park, Joo Seop ; Degraff, David. / FOXA1, GATA3 and PPARIγ Cooperate to drive luminal subtype in bladder cancer : A molecular analysis of established human cell lines. In: Scientific reports. 2016 ; Vol. 6.
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abstract = "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 PPARI 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 PPARI drive luminal cell fate.",
author = "Joshua Warrick and Vonn Walter and Hironobu Yamashita and Eunah Chung and Lauren Shuman and Amponsa, {Vasty Osei} and Zongyu Zheng and Wilson Chan and Tiffany Whitcomb and Feng Yue and Tejaswi Iyyanki and Yuka Imamura and Kaag, {Matthew G.} and Wansong Guo and Jay Raman and Park, {Joo Seop} and David Degraff",
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FOXA1, GATA3 and PPARIγ Cooperate to drive luminal subtype in bladder cancer : A molecular analysis of established human cell lines. / Warrick, Joshua; Walter, Vonn; Yamashita, Hironobu; Chung, Eunah; Shuman, Lauren; Amponsa, Vasty Osei; Zheng, Zongyu; Chan, Wilson; Whitcomb, Tiffany; Yue, Feng; Iyyanki, Tejaswi; Imamura, Yuka; Kaag, Matthew G.; Guo, Wansong; Raman, Jay; Park, Joo Seop; Degraff, David.

In: Scientific reports, Vol. 6, 38531, 07.12.2016.

Research output: Contribution to journalArticle

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T1 - FOXA1, GATA3 and PPARIγ Cooperate to drive luminal subtype in bladder cancer

T2 - A molecular analysis of established human cell lines

AU - Warrick, Joshua

AU - Walter, Vonn

AU - Yamashita, Hironobu

AU - Chung, Eunah

AU - Shuman, Lauren

AU - Amponsa, Vasty Osei

AU - Zheng, Zongyu

AU - Chan, Wilson

AU - Whitcomb, Tiffany

AU - Yue, Feng

AU - Iyyanki, Tejaswi

AU - Imamura, Yuka

AU - Kaag, Matthew G.

AU - Guo, Wansong

AU - Raman, Jay

AU - Park, Joo Seop

AU - Degraff, David

PY - 2016/12/7

Y1 - 2016/12/7

N2 - 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 PPARI 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 PPARI drive luminal cell fate.

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