Signal pathways in up-regulation of chemokines by tyrosine kinase MER/NYK in prostate cancer cells

Yi Mi Wu, Dan R. Robinson, Hsing Jien Kung

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

The AXL/UFO family of tyrosine kinases is characterized by a common N-CAM (neural adhesion molecule)-related extracellular domain and a common ligand, GAS6 (growth arrest-specific protein 6). Family members are prone to transcriptional regulation and carry out diverse functions including the regulation of cell adhesion, migration, phagocytosis, and survival. In this report, we describe a new role of MER/N-CAM-related kinase (NYK), a member of the AXL family of kinases, in the up-regulation of chemokines in prostate cancer cells. We show that NYK has elevated expression in a subset of tumor specimens and prostate cancer cell lines. Activation of NYK in the prostate cancer cell line DU145 does not cause a mitogenic effect; instead, it causes a differentiation phenotype. Microarray analysis revealed that NYK is a strong inducer of endocrine factors including interleukin (IL)-8 and several other angiogenic CXC chemokines as well as bone morphogenic factors. The dramatic increase of IL-8 expression is seen at both transcriptional and posttranscriptional levels. The downstream signals engaged by NYK were characterized, and those responsible for the up-regulation of IL-8 transcription were defined. In contrast to IL-1α, NYK-induced up-regulation of IL-8 in DU145 depends on the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase/Jun/Fos pathway, but not phosphoinositide 3′-kinase/ nuclear factor-κB. These data define a new function of the AXL family of kinases and suggest a potential role of NYK in prostate cancer progression.

Original languageEnglish
Pages (from-to)7311-7320
Number of pages10
JournalCancer Research
Volume64
Issue number20
DOIs
Publication statusPublished - Oct 15 2004
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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