title: On a FOX hunt: functions of FOX transcriptional regulators in bladder cancer.
abstract: Genomic and transcriptional studies have identified discrete molecular subtypes of bladder cancer. These observations could be the starting point to identify new treatments. Several members of the forkhead box (FOX) superfamily of transcription factors have been found to be differentially expressed in the different bladder cancer subtypes. In addition, the FOXA protein family are key regulators of embryonic bladder development and patterning. Both experimental and clinical data support a role for FOXA1 and FOXA2 in urothelial carcinoma. FOXA1 is expressed in embryonic and adult urothelium and its expression is altered in urothelial carcinomas and across disparate molecular bladder cancer subtypes. FOXA2 is normally absent from the adult urothelium, but developmental studies identified FOXA2 as a marker of a transient urothelial progenitor cell population during bladder development. Studies also implicate FOXA2 in bladder cancer and several other FOX proteins might be involved in development and/or progression of this disease; for example, FOXA1 and FOXO3A have been associated with clinical patient outcomes. Future studies should investigate to what extent and by which mechanisms FOX proteins might be directly involved in bladder cancer pathogenesis and treatment responses.
authors.affiliation: Department of Pathology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033, USA.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Department of Pathology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033, USA.
authors.forename: Vasty Osei
authors.initials: VO
authors.lastname: Amponsa
authors.affiliation: Department of Pathology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033, USA.
authors.forename: Joshua I
authors.initials: JI
authors.lastname: Warrick
authors.affiliation: Department of Pathology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033, USA.
authors.forename: Zongyu
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Urologic Surgery, Vanderbilt University Medical Center, 21st Avenue South, Nashville, Tennessee 37232, USA.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Clark
authors.affiliation: Department of Surgery, Division of Urology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033, USA.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.affiliation: Departments of Pathology and Urology, New York University College of Medicine, New York, New York 10016, USA.
authors.forename: Xue-Ru
authors.initials: XR
authors.lastname: Wu
authors.affiliation: Department of Urology, Columbia University, New York, New York 10032, USA.
authors.forename: Cathy
authors.initials: C
authors.lastname: Mendelsohn
authors.affiliation: Department of Pathology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033, USA.|Department of Surgery, Division of Urology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033, USA.|Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: DeGraff
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C496499:FOXA1 protein, human; D051858:Forkhead Transcription Factors; D051541:Hepatocyte Nuclear Factor 3-alpha