SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium

Rebecca Marlow, Phyllis Strickland, Shin Lee Ji, Xinyan Wu, Milana PeBenito, Mikhail Binnewies, Elizabeth K. Le, Angel Moran, Hector Macias, Robert D. Cardiff, Saraswati Sukumar, Lindsay Hinck

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

The genes encoding Slits and their Robo receptors are silenced in many types of cancer, including breast, suggesting a role for this signaling pathway in suppressing tumorigenesis. The molecular mechanism underlying these tumor-suppressive effects has not been delineated. Here, we show that loss of Slits, or their Robo1 receptor, in murine mammary gland or human breast carcinoma cells results in coordinate up-regulation of the Sdf1 and Cxcr4 signaling axis, specifically within mammary epithelium. This is accompanied by hyperplastic changes in cells and desmoplastic alterations in the surrounding stroma. A similar inverse correlation between Slit and Cxcr4 expression is identified in human breast tumor tissues. Furthermore, we show in a xenograft model that Slit overexpression down-regulates CXCR4 and dominantly suppresses tumor growth. These studies classify Slits as negative regulators of Sdf1 and Cxcr4 and identify a molecular signature in hyperplastic breast lesions that signifies inappropriate up-regulation of key prometastatic genes.

Original languageEnglish (US)
Pages (from-to)7819-7827
Number of pages9
JournalCancer Research
Volume68
Issue number19
DOIs
StatePublished - Oct 1 2008
Externally publishedYes

Fingerprint

Breast
Epithelium
Breast Neoplasms
Up-Regulation
Growth
Neoplasms
Human Mammary Glands
Heterografts
Genes
Carcinogenesis
Down-Regulation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Marlow, R., Strickland, P., Ji, S. L., Wu, X., PeBenito, M., Binnewies, M., ... Hinck, L. (2008). SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium. Cancer Research, 68(19), 7819-7827. https://doi.org/10.1158/0008-5472.CAN-08-1357

SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium. / Marlow, Rebecca; Strickland, Phyllis; Ji, Shin Lee; Wu, Xinyan; PeBenito, Milana; Binnewies, Mikhail; Le, Elizabeth K.; Moran, Angel; Macias, Hector; Cardiff, Robert D.; Sukumar, Saraswati; Hinck, Lindsay.

In: Cancer Research, Vol. 68, No. 19, 01.10.2008, p. 7819-7827.

Research output: Contribution to journalArticle

Marlow, R, Strickland, P, Ji, SL, Wu, X, PeBenito, M, Binnewies, M, Le, EK, Moran, A, Macias, H, Cardiff, RD, Sukumar, S & Hinck, L 2008, 'SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium', Cancer Research, vol. 68, no. 19, pp. 7819-7827. https://doi.org/10.1158/0008-5472.CAN-08-1357
Marlow, Rebecca ; Strickland, Phyllis ; Ji, Shin Lee ; Wu, Xinyan ; PeBenito, Milana ; Binnewies, Mikhail ; Le, Elizabeth K. ; Moran, Angel ; Macias, Hector ; Cardiff, Robert D. ; Sukumar, Saraswati ; Hinck, Lindsay. / SLITs suppress tumor growth in vivo by silencing Sdf1/Cxcr4 within breast epithelium. In: Cancer Research. 2008 ; Vol. 68, No. 19. pp. 7819-7827.
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