+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis

RANK induces epithelial-mesenchymal transition and stemness in human mammary epithelial cells and promotes tumorigenesis and metastasis

Cancer Research 72(11): 2879-2888

Paracrine signaling through receptor activator of NF-κB (RANK) pathway mediates the expansion of mammary epithelia that occurs during pregnancy, and activation of RANK pathway promotes mammary tumorigenesis in mice. In this study we extend these previous data to human cells and show that the RANK pathway promotes the development of mammary stem cells and breast cancer. Overexpression of RANK (FL-RANK) in a panel of tumoral and normal human mammary cells induces the expression of breast cancer stem and basal/stem cell markers. High levels of RANK in untransformed MCF10A cells induce changes associated with both stemness and transformation, including mammary gland reconstitution, epithelial-mesenchymal transition (EMT), increased migration, and anchorage-independent growth. In addition, spheroids of RANK overexpressing MCF10A cells display disrupted acinar formation, impair growth arrest and polarization, and luminal filling. RANK overexpression in tumor cells with nonfunctional BRCA1 enhances invasiveness in acinar cultures and increases tumorigenesis and metastasis in immunodeficient mice. High levels of RANK were found in human primary breast adenocarcinomas that lack expression of the hormone receptors, estrogen and progesterone, and in tumors with high pathologic grade and proliferation index; high RANK/RANKL expression was significantly associated with metastatic tumors. Together, our findings show that RANK promotes tumor initiation, progression, and metastasis in human mammary epithelial cells by increasing the population of CD44(+)CD24(-) cells, inducing stemness and EMT. These results suggest that RANK expression in primary breast cancer associates with poor prognosis.

(PDF emailed within 0-6 h: $19.90)

Accession: 055333129

Download citation: RISBibTeXText

PMID: 22496457

DOI: 10.1158/0008-5472.CAN-12-0044

Related references

Inhibition of ubiquitin-specific protease 34 (USP34) induces epithelial-mesenchymal transition and promotes stemness in mammary epithelial cells. Cellular Signalling 36: 230-239, 2017

Vimentin intermediate filament expression in mammary gland epithelial cells induces changes in cell shape and motility Metastasis and the epithelial/mesenchymal transition. Molecular Biology of the Cell 12(Supplement): 53a, 2001

Expression of activated M-Ras in a murine mammary epithelial cell line induces epithelial-mesenchymal transition and tumorigenesis. Oncogene 23(6): 1187-1196, 12 February, 2004

miR-409-3p/-5p promotes tumorigenesis, epithelial-to-mesenchymal transition, and bone metastasis of human prostate cancer. Clinical Cancer Research 20(17): 4636-4646, 2015

siRNA gelsolin knockdown induces epithelial-mesenchymal transition with a cadherin switch in human mammary epithelial cells. International Journal of Cancer 118(7): 1680-1691, 2005

Hydrogen peroxide promotes epithelial to mesenchymal transition and stemness in human malignant mesothelioma cells. Asian Pacific Journal of Cancer Prevention 14(6): 3625-3630, 2014

The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-beta signaling. Journal of Clinical Investigation 119(9): 2678-2690, 2009

Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 20(5): 576-590, 2012

Interferon alpha-inducible protein 27 promotes epithelial-mesenchymal transition and induces ovarian tumorigenicity and stemness. Journal of Surgical Research 193(1): 255-264, 2015

Arachidonic acid promotes epithelial-to-mesenchymal-like transition in mammary epithelial cells MCF10A. European Journal of Cell Biology 89(6): 476-488, 2010

Revisiting epithelial-mesenchymal transition in cancer metastasis: the connection between epithelial plasticity and stemness. Molecular Oncology 11(7): 792-804, 2017

ESX induces transformation and functional epithelial to mesenchymal transition in MCF-12A mammary epithelial cells. Oncogene 23(9): 1766-1779, 4 March, 2004

Constitutive expression of Bcl-2 induces epithelial-Mesenchymal transition in mammary epithelial cells. Bmc Cancer 15(): 476-476, 2016

EBV-miR-BART8-3p induces epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma cells through activating NF-κB and Erk1/2 pathways. Journal of Experimental & Clinical Cancer Research 37(1): 283-283, 2018

Overexpression of c-myc induces epithelial mesenchymal transition in mammary epithelial cells. Cancer Letters 293(2): 230-239, 2010