A developmentally regulated inducer of EMT, LBX1, contributes to breast cancer progression

Min Yu; Gromoslaw A. Smolen; Jianmin Zhang; Ben Wittner; Benjamin J. Schott; Elena Brachtel; Sridhar Ramaswamy; Shyamala Maheswaran; Daniel A. Haber

doi:10.1101/gad.1809309

A developmentally regulated inducer of EMT, LBX1, contributes to breast cancer progression

¹Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
²Howard Hughes Medical Institute, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA;
³Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA

Abstract

Epithelial-to-mesenchymal transition (EMT) plays an important role during normal embryogenesis, and it has been implicated in cancer invasion and metastasis. Here, we report that Ladybird homeobox 1 (LBX1), a developmentally regulated homeobox gene, directs expression of the known EMT inducers ZEB1, ZEB2, Snail1, and transforming growth factor β2 (TGFB2). In mammary epithelial cells, overexpression of LBX1 leads to morphological transformation, expression of mesenchymal markers, enhanced cell migration, increased CD44^high/CD24^low progenitor cell population, and tumorigenic cooperation with known oncogenes. In human breast cancer, LBX1 is up-regulated in the unfavorable estrogen receptor (ER)/progesterone (PR)/HER2 triple-negative basal-like subtype. Thus, aberrant expression of LBX1 may lead to the activation of a developmentally regulated EMT pathway in human breast cancer.

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Footnotes

↵4 Corresponding author.

E-MAIL haber{at}helix.mgh.harvard.edu; FAX (617) 724-6919.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1809309.
Supplemental material is available at http://www.genesdev.org.
- Received April 8, 2009.
- Accepted June 16, 2009.
Freely available online through the Genes & Development Open Access option.