Regulation of C-X-C chemokine gene expression by keratin 17 and hnRNP K in skin tumor keratinocytes

Byung Min Chung, Artem Arutyunov, Erika Ilagan, Nu Yao, Marsha Wills-Karp, Pierre A. Coulombe

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)613-627
Number of pages15
JournalJournal of Cell Biology
Volume208
Issue number5
DOIs
StatePublished - 2015

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Heterogeneous-Nuclear Ribonucleoprotein K
Keratin-17
CXC Chemokines
Keratinocytes
Gene Expression
Skin
Neoplasms
Carcinogenesis
Foster Home Care
RNA-Binding Proteins
Intermediate Filaments
Phosphotransferases
Ligands
Inflammation
Messenger RNA
Growth

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

Regulation of C-X-C chemokine gene expression by keratin 17 and hnRNP K in skin tumor keratinocytes. / Chung, Byung Min; Arutyunov, Artem; Ilagan, Erika; Yao, Nu; Wills-Karp, Marsha; Coulombe, Pierre A.

In: Journal of Cell Biology, Vol. 208, No. 5, 2015, p. 613-627.

Research output: Contribution to journalArticle

Chung, Byung Min ; Arutyunov, Artem ; Ilagan, Erika ; Yao, Nu ; Wills-Karp, Marsha ; Coulombe, Pierre A. / Regulation of C-X-C chemokine gene expression by keratin 17 and hnRNP K in skin tumor keratinocytes. In: Journal of Cell Biology. 2015 ; Vol. 208, No. 5. pp. 613-627.
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