title: Regulation of C-X-C chemokine gene expression by keratin 17 and hnRNP K in skin tumor keratinocytes.
abstract: High levels of the intermediate filament keratin 17 (K17) correlate with a poor prognosis for several types of epithelial tumors. However, the causal relationship and underlying mechanisms remain undefined. A recent study suggested that K17 promotes skin tumorigenesis by fostering a specific type of inflammation. We report here that K17 interacts with the RNA-binding protein hnRNP K, which has also been implicated in cancer. K17 is required for the cytoplasmic localization of hnRNP K and for its role in regulating the expression of multiple pro-inflammatory mRNAs. Among these are the CXCR3 ligands CXCL9, CXCL10, and CXCL11, which together form a signaling axis with an established role in tumorigenesis. The K17-hnRNP K partnership is regulated by the ser/thr kinase RSK and required for CXCR3-dependent tumor cell growth and invasion. These findings functionally integrate K17, hnRNP K, and gene expression along with RSK and CXCR3 signaling in a keratinocyte-autonomous axis and provide a potential basis for their implication in tumorigenesis.
authors.affiliation: Department of Biochemistry and Molecular Biology and Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health; and Department of Biological Chemistry, Department of Dermatology, and Department of Oncology, School of Medicine, Johns Hopkins University, MD 21205.
authors.forename: Byung Min
authors.initials: BM
authors.lastname: Chung
authors.affiliation: Department of Biochemistry and Molecular Biology and Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health; and Department of Biological Chemistry, Department of Dermatology, and Department of Oncology, School of Medicine, Johns Hopkins University, MD 21205.
authors.forename: Artem
authors.initials: A
authors.lastname: Arutyunov
authors.affiliation: Department of Biochemistry and Molecular Biology and Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health; and Department of Biological Chemistry, Department of Dermatology, and Department of Oncology, School of Medicine, Johns Hopkins University, MD 21205.
authors.forename: Erika
authors.initials: E
authors.lastname: Ilagan
authors.affiliation: Department of Biochemistry and Molecular Biology and Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health; and Department of Biological Chemistry, Department of Dermatology, and Department of Oncology, School of Medicine, Johns Hopkins University, MD 21205.
authors.forename: Nu
authors.initials: N
authors.lastname: Yao
authors.affiliation: Department of Biochemistry and Molecular Biology and Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health; and Department of Biological Chemistry, Department of Dermatology, and Department of Oncology, School of Medicine, Johns Hopkins University, MD 21205.
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
authors.affiliation: Department of Biochemistry and Molecular Biology and Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health; and Department of Biological Chemistry, Department of Dermatology, and Department of Oncology, School of Medicine, Johns Hopkins University, MD 21205 Department of Biochemistry and Molecular Biology and Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health; and Department of Biological Chemistry, Department of Dermatology, and Department of Oncology, School of Medicine, Johns Hopkins University, MD 21205 Department of Biochemistry and Molecular Biology and Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health; and Department of Biological Chemistry, Department of Dermatology, and Department of Oncology, School of Medicine, Johns Hopkins University, MD 21205 Department of Biochemistry and Molecular Biology and Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health; and Department of Biological Chemistry, Department of Dermatology, and Department of Oncology, School of Medicine, Johns Hopkins University, MD 21205 coulombe@jhu.edu.
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Coulombe
mesh_terms: D000818:Animals; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007633:Keratins / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D054367:Receptors, CXCR3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C515187:CXCR3 protein, human; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; C118917:Krt17 protein, mouse; D009363:Neoplasm Proteins; D054367:Receptors, CXCR3; D007633:Keratins