PTX3 gene activation in EGF-induced head and neck cancer cell metastasis

Wei Chiao Chang, Shuo Lun Wu, Wan Chen Huang, Jinn Yuan Hsu, Shih Hung Chan, Ju Ming Wang, Jhih Peng Tsai, Ben Kuen Chen

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Overexpression of the epidermal growth factor (EGF) receptor (EGFR) is associated with enhanced invasion and metastasis in head and neck squamous cell carcinoma (HNSCC). Long Pentraxin PTX3 is involved in immune escape in cancer cells. Here, we identified PTX3 as a promoting factor that mediates EGF-induced HNSCC metastasis. EGF-induced PTX3 transcriptional activation is via the binding of c-Jun to the activator protein (AP)-1 binding site of the PTX3 promoter. PI3K/Akt and NF-κB were essential for the PTX3 activation. EGF-induced PTX3 expression was blocked in c-Jun- and NF-κB-knockdown cells. EGF-mediated PTX3 secretion resulted in the enhancement of cell migration and invasion, and interactions between cancer and endothelial cells. The tail-vein injection animal model revealed that depletion of PTX3 decreased EGF-primed tumor cell metastatic seeding of the lungs. In addition, fibronectin, matrix metalloproteinase-9 (MMP9) and E-cadherin were essential components in EGFR/PTX3-mediated cancer metastasis. In conclusion, PI3K/Akt and NF-κB-dependent regulation of AP-1 mediates PTX3 transcriptional responses to EGF. Autocrine production of EGF-induced PTX3 in turn induces metastatic molecules, activating inflammatory cascades and metastasis.

Original languageEnglish
Pages (from-to)7741-7757
Number of pages17
JournalOncotarget
Volume6
Issue number10
Publication statusPublished - 2015

Keywords

  • Cancer metastasis
  • EGF
  • PTX3

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Chang, W. C., Wu, S. L., Huang, W. C., Hsu, J. Y., Chan, S. H., Wang, J. M., Tsai, J. P., & Chen, B. K. (2015). PTX3 gene activation in EGF-induced head and neck cancer cell metastasis. Oncotarget, 6(10), 7741-7757.