Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8

Kongming Wu, Sanjay Katiyar, Anping Li, Manran Liu, Xiaoming Ju, Vladimir M. Popov, Xuanmao Jiao, Michael P. Lisanti, Antonella Casola, Richard G. Pestell

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Oncogene-mediated signaling to the host environment induces a subset of cytokines and chemokines. The Drosophila Dac gene promotes migration of the morphogenetic furrow during eye development. Expression of the cell-fate determination factor Dachshund (DACH1) was lost in poor prognosis invasive breast cancer. Mouse embryo fibroblasts derived from Dach1-/- mice demonstrated endogenous Dach1 constitutively represses cellular migration. DACH1 inhibited cellular migration and invasion of oncogene (Ras, Myc, ErbB2, c-Raf)-transformed human breast epithelial cells. An unbiased proteomic analysis identified and immunoneutralizing antibody and reconstitution experiments demonstrated IL-8 is a critical target of DACH1 mediating breast cancer cellular migration and metastasis in vivo. DACH1 bound the endogenous IL-8 promoter in ChIP assays and repressed the IL-8 promoter through the AP-1 and NF-κB binding sites. Collectively, our data identify a pathway by which an endogenous cell-fate determination factor blocks oncogene-dependent tumor metastasis via a key heterotypic mediator.

Original languageEnglish (US)
Pages (from-to)6924-6929
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number19
DOIs
StatePublished - May 13 2008

Fingerprint

Interleukin-8
Oncogenes
Breast Neoplasms
Neoplasm Metastasis
myc Genes
ras Genes
Transcription Factor AP-1
Chemokines
Proteomics
Drosophila
Breast
Embryonic Structures
Fibroblasts
Epithelial Cells
Binding Sites
Cytokines
Antibodies
Genes
Neoplasms

Keywords

  • DACH1
  • Metastasis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8. / Wu, Kongming; Katiyar, Sanjay; Li, Anping; Liu, Manran; Ju, Xiaoming; Popov, Vladimir M.; Jiao, Xuanmao; Lisanti, Michael P.; Casola, Antonella; Pestell, Richard G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 19, 13.05.2008, p. 6924-6929.

Research output: Contribution to journalArticle

Wu, Kongming ; Katiyar, Sanjay ; Li, Anping ; Liu, Manran ; Ju, Xiaoming ; Popov, Vladimir M. ; Jiao, Xuanmao ; Lisanti, Michael P. ; Casola, Antonella ; Pestell, Richard G. / Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 19. pp. 6924-6929.
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