title: Distinct Metabolic Signature of Human Bladder Cancer Cells Carrying an Impaired Fanconi Anemia Tumor-Suppressor Signaling Pathway.
abstract: Metabolic profiling has great potential to help the diagnosis and prognosis of cancer patients. Fanconi Anemia (FA) tumor-suppressor signaling has been instrumental in understanding human tumorigenesis. However, this instrumental understanding has never been demonstrated at the metabolic level. Here, we show that impaired FA signaling can lead cells to exhibit metabolic signatures of tumorigenesis. This is consistent with our original studies of the roles of FA signaling in suppressing non-FA tumorigenesis at functional and genetic levels. Using ultraperformance liquid chromatography-mass spectroscopy and gas chromatography-mass spectrometry, we characterized metabolic alterations in bladder cancer cells carrying an intact or impaired FA pathway. The latter was obtained by ectopically expressing FAVL (FAVL-high), which we previously found to be capable of inactivating FA signaling. A total of 18 metabolites, end products of cell proliferation or apoptosis, were significantly different between FAVL-high and -low cells. Methionine, phenylalanine, and threonine, resulting from a tumorigenic process, were substantially increased in FAVL-high cells. With this study, we achieved genomic, functional, and metabolomic characterization of the roles of FA signaling in the development of human cancer. Furthermore, this study provides novel insights into how to translate FA basic research into strategies for producing effective biomarkers in human cancer diagnosis and prognosis.
authors.affiliation: University of Hawaii Cancer Center, University of Hawaii , Honolulu, Hawaii, 96813 United States.
authors.forename: Jayabal
authors.initials: J
authors.lastname: Panneerselvam
authors.affiliation: University of Hawaii Cancer Center, University of Hawaii , Honolulu, Hawaii, 96813 United States.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.affiliation: University of Hawaii Cancer Center, University of Hawaii , Honolulu, Hawaii, 96813 United States.
authors.forename: Raymond
authors.initials: R
authors.lastname: Che
authors.affiliation: University of Hawaii Cancer Center, University of Hawaii , Honolulu, Hawaii, 96813 United States.
authors.forename: Mingming
authors.initials: M
authors.lastname: Su
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation , Rochester, Minnesota, 55905 United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: University of Hawaii Cancer Center, University of Hawaii , Honolulu, Hawaii, 96813 United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: University of Hawaii Cancer Center, University of Hawaii , Honolulu, Hawaii, 96813 United States.
authors.forename: Peiwen
authors.initials: P
authors.lastname: Fei
mesh_terms: D017398:Alternative Splicing; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002853:Chromatography, Liquid; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D052240:Fanconi Anemia Complementation Group L Protein / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D013058:Mass Spectrometry; D055442:Metabolome; D008715:Methionine / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D019076:Transgenes
chemical_list: D020033:Protein Isoforms; D013912:Threonine; D010649:Phenylalanine; D008715:Methionine; C499908:FANCL protein, human; D052240:Fanconi Anemia Complementation Group L Protein
keywords: FA pathway; FAVL; bladder cancer; cell proliferation; metabolomics