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.
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Authors | Byung Min Chung, Artem Arutyunov, Erika Ilagan, Nu Yao, Marsha Wills-Karp, Pierre A Coulombe |
Journal | The Journal of cell biology
(J Cell Biol)
Vol. 208
Issue 5
Pg. 613-27
(Mar 02 2015)
ISSN: 1540-8140 [Electronic] United States |
PMID | 25713416
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2015 Chung et al. |
Chemical References |
- CXCR3 protein, human
- Chemokines, CXC
- Cxcr3 protein, mouse
- Heterogeneous-Nuclear Ribonucleoprotein K
- Krt17 protein, mouse
- Neoplasm Proteins
- Receptors, CXCR3
- Keratins
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Topics |
- Animals
- Chemokines, CXC
(biosynthesis, genetics)
- Gene Expression Regulation, Neoplastic
- HeLa Cells
- Heterogeneous-Nuclear Ribonucleoprotein K
(genetics, metabolism)
- Humans
- Keratinocytes
(metabolism)
- Keratins
(genetics, metabolism)
- Mice, Knockout
- Neoplasm Proteins
(genetics, metabolism)
- Receptors, CXCR3
(genetics, metabolism)
- Signal Transduction
(genetics)
- Skin Neoplasms
(genetics, metabolism, pathology)
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