LRIG1 opposes epithelial-To-mesenchymal transition and inhibits invasion of basal-like breast cancer cells

N. Yokdang, J. Hatakeyama, J. H. Wald, C. Simion, J. D. Tellez, D. Z. Chang, M. M. Swamynathan, M. Chen, W. J. Murphy, K. L. Carraway, C. Sweeney

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

LRIG1 (leucine-rich repeat and immunoglobulin-like domain containing), a member of the LRIG family of transmembrane leucine-rich repeat-containing proteins, is a negative regulator of receptor tyrosine kinase signaling and a tumor suppressor. LRIG1 expression is broadly decreased in human cancer and in breast cancer and low expression of LRIG1 has been linked to decreased relapse-free survival. Recently, low expression of LRIG1 was revealed to be an independent risk factor for breast cancer metastasis and death. These findings suggest that LRIG1 may oppose breast cancer cell motility and invasion, cellular processes that are fundamental to metastasis. However, very little is known of LRIG1 function in this regard. In this study, we demonstrate that LRIG1 is downregulated during epithelial-To-mesenchymal transition (EMT) of human mammary epithelial cells, suggesting that LRIG1 expression may represent a barrier to EMT. Indeed, depletion of endogenous LRIG1 in human mammary epithelial cells expands the stem cell population, augments mammosphere formation and accelerates EMT. Conversely, expression of LRIG1 in highly invasive Basal B breast cancer cells provokes a mesenchymal-To-epithelial transition accompanied by a dramatic suppression of tumorsphere formation and a striking loss of invasive growth in three-dimensional culture. LRIG1 expression perturbs multiple signaling pathways and represses markers and effectors of the mesenchymal state. Furthermore, LRIG1 expression in MDA-MB-231 breast cancer cells significantly slows their growth as tumors, providing the first in vivo evidence that LRIG1 functions as a growth suppressor in breast cancer.

Original languageEnglish (US)
Pages (from-to)2932-2947
Number of pages16
JournalOncogene
Volume35
Issue number22
DOIs
StatePublished - Jun 2 2016

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Epithelial-Mesenchymal Transition
Breast Neoplasms
Breast
Growth
Epithelial Cells
Neoplasm Metastasis
Receptor Protein-Tyrosine Kinases
Leucine
Cell Movement
Neoplasms
Stem Cells
Down-Regulation
Recurrence
Survival
Population

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Yokdang, N., Hatakeyama, J., Wald, J. H., Simion, C., Tellez, J. D., Chang, D. Z., ... Sweeney, C. (2016). LRIG1 opposes epithelial-To-mesenchymal transition and inhibits invasion of basal-like breast cancer cells. Oncogene, 35(22), 2932-2947. https://doi.org/10.1038/onc.2015.345

LRIG1 opposes epithelial-To-mesenchymal transition and inhibits invasion of basal-like breast cancer cells. / Yokdang, N.; Hatakeyama, J.; Wald, J. H.; Simion, C.; Tellez, J. D.; Chang, D. Z.; Swamynathan, M. M.; Chen, M.; Murphy, W. J.; Carraway, K. L.; Sweeney, C.

In: Oncogene, Vol. 35, No. 22, 02.06.2016, p. 2932-2947.

Research output: Contribution to journalArticle

Yokdang, N, Hatakeyama, J, Wald, JH, Simion, C, Tellez, JD, Chang, DZ, Swamynathan, MM, Chen, M, Murphy, WJ, Carraway, KL & Sweeney, C 2016, 'LRIG1 opposes epithelial-To-mesenchymal transition and inhibits invasion of basal-like breast cancer cells', Oncogene, vol. 35, no. 22, pp. 2932-2947. https://doi.org/10.1038/onc.2015.345
Yokdang N, Hatakeyama J, Wald JH, Simion C, Tellez JD, Chang DZ et al. LRIG1 opposes epithelial-To-mesenchymal transition and inhibits invasion of basal-like breast cancer cells. Oncogene. 2016 Jun 2;35(22):2932-2947. https://doi.org/10.1038/onc.2015.345
Yokdang, N. ; Hatakeyama, J. ; Wald, J. H. ; Simion, C. ; Tellez, J. D. ; Chang, D. Z. ; Swamynathan, M. M. ; Chen, M. ; Murphy, W. J. ; Carraway, K. L. ; Sweeney, C. / LRIG1 opposes epithelial-To-mesenchymal transition and inhibits invasion of basal-like breast cancer cells. In: Oncogene. 2016 ; Vol. 35, No. 22. pp. 2932-2947.
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