title: Characterization of SLC22A18 as a tumor suppressor and novel biomarker in colorectal cancer.
abstract: SLC22A18, solute carrier family 22, member 18, has been proposed to function as a tumor suppressor based on its chromosomal location at 11p15.5, mutations and aberrant splicing in several types of cancer and down-regulation in glioblastoma. In this study, we sought to demonstrate the significance of SLC22A18 as a tumor suppressor in colorectal cancer (CRC) and provide mechanistic bases for its function. We first showed that the expression of SLC22A18 is significantly down-regulated in tumor tissues using matched normal-tumor samples from CRC patients. This finding was also supported by publically accessible data from The Cancer Genome Atlas (TCGA). Functionally, SLC22A18 inhibits colony formation and induces of G2/M arrest consistent with being a tumor suppressor. Interestingly, suppression of KRAS by RNA interference promotes SLC22A18 expression, and expression of SLC22A18 in turn inhibits KRAS(G12D)-mediated anchorage independent growth of NIH3T3 cells indicating a mutual negative interaction. Finally, we evaluated diagnostic and prognostic values of SLC22A18 using clinical and gene expression data from TCGA which revealed a significantly worse long-term prognosis for patients with low level SLC22A18 expression. In sum, we established SLC22A18 as a tumor suppressor in colon epithelial cells and propose that SLC22A18 is potentially a marker of diagnostic and prognostic values.
authors.affiliation: Ewha Research Center for Systems Biology, Seoul, Korea.|Department of Life Science, Ewha Womans University, Seoul, Korea.
authors.forename: Yeonjoo
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Ewha Research Center for Systems Biology, Seoul, Korea.|Department of Life Science, Ewha Womans University, Seoul, Korea.
authors.forename: Yukyung
authors.initials: Y
authors.lastname: Jun
authors.affiliation: Ewha Research Center for Systems Biology, Seoul, Korea.|Department of Life Science, Ewha Womans University, Seoul, Korea.
authors.forename: Hee-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Ewha Research Center for Systems Biology, Seoul, Korea.|Department of Life Science, Ewha Womans University, Seoul, Korea.
authors.forename: Suyeon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Ewha Research Center for Systems Biology, Seoul, Korea.|Department of Life Science, Ewha Womans University, Seoul, Korea.
authors.forename: Yeonhwa
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Ewha Research Center for Systems Biology, Seoul, Korea.|Department of Life Science, Ewha Womans University, Seoul, Korea.
authors.forename: Juhee
authors.initials: J
authors.lastname: Keum
authors.affiliation: Samsung Biomedical Research Institute, Seoul, Korea.
authors.forename: Yeo Song
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yong Beom
authors.initials: YB
authors.lastname: Cho
authors.affiliation: Ewha Research Center for Systems Biology, Seoul, Korea.|Department of Life Science, Ewha Womans University, Seoul, Korea.
authors.forename: Sanghyuk
authors.initials: S
authors.lastname: Lee
authors.affiliation: Ewha Research Center for Systems Biology, Seoul, Korea.|Department of Life Science, Ewha Womans University, Seoul, Korea.
authors.forename: Jaesang
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D030541:Databases, Genetic; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D014162:Transfection; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D027701:Organic Cation Transport Proteins; C111653:SLC22A18 protein, human; D025521:Tumor Suppressor Proteins; D016283:Proto-Oncogene Proteins p21(ras)
keywords: G2/M arrest; KRAS; SLC22A18; colorectal cancer; tumor suppressor