Article pubs.acs.org/jpr
Distinct Metabolic Signature of Human Bladder Cancer Cells Carrying an Impaired Fanconi Anemia Tumor-Suppressor Signaling Pathway Jayabal Panneerselvam,† Guoxiang Xie,† Raymond Che,† Mingming Su,† Jun Zhang,‡ Wei Jia,† and Peiwen Fei*,† †
University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii, 96813 United States Department of Laboratory Medicine and Pathology, Mayo Clinic Foundation, Rochester, Minnesota, 55905 United States
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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. KEYWORDS: metabolomics, bladder cancer, FA pathway, FAVL, cell proliferation
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INTRODUCTION Metabolomics is the study of the small molecule composition (metabolites
