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

Genes Dev. 2009 Aug 1;23(15):1737-42. doi: 10.1101/gad.1809309.

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 beta2 (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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / physiopathology*
  • CD24 Antigen / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Disease Progression*
  • Gene Expression Regulation, Neoplastic*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Hyaluronan Receptors / metabolism
  • Mammary Glands, Human / cytology
  • Mammary Glands, Human / metabolism
  • Oncogenes / physiology
  • Organic Cation Transport Proteins / metabolism*
  • Repressor Proteins / metabolism
  • Snail Family Transcription Factors
  • Stem Cells / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta2 / metabolism
  • Up-Regulation
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • CD24 Antigen
  • Homeodomain Proteins
  • Hyaluronan Receptors
  • LBX1 protein, human
  • Organic Cation Transport Proteins
  • Repressor Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TGFB2 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta2
  • ZEB1 protein, human
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1
  • solute carrier family 22 (organic cation transporter), member 3