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

doi:10.1073/pnas.0802085105

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

Pediatrics

Research output: Contribution to journal › Article › peer-review

82 Scopus citations

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 language	English (US)
Pages (from-to)	6924-6929
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	105
Issue number	19
DOIs	https://doi.org/10.1073/pnas.0802085105
State	Published - May 13 2008

Keywords

DACH1
Metastasis

ASJC Scopus subject areas

General

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10.1073/pnas.0802085105

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Wu, K., Katiyar, S., Li, A., Liu, M., Ju, X., Popov, V. M., Jiao, X., Lisanti, M. P., Casola, A., & Pestell, R. G. (2008). Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8. Proceedings of the National Academy of Sciences of the United States of America, 105(19), 6924-6929. https://doi.org/10.1073/pnas.0802085105

Wu, K, Katiyar, S, Li, A, Liu, M, Ju, X, Popov, VM, Jiao, X, Lisanti, MP, Casola, A & Pestell, RG 2008, 'Dachshund inhibits oncogene-induced breast cancer cellular migration and invasion through suppression of interleukin-8', Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 19, pp. 6924-6929. https://doi.org/10.1073/pnas.0802085105

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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.",

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AU - Ju, Xiaoming

AU - Popov, Vladimir M.

AU - Jiao, Xuanmao

AU - Lisanti, Michael P.

AU - Casola, Antonella

AU - Pestell, Richard G.

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N2 - 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.

AB - 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.

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KW - Metastasis

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

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