MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells

Lourdes Sánchez-Cid, Mònica Pons, Juan José Lozano, Nuria Rubio, Marta Guerra-Rebollo, Aroa Soriano, Laia Paris-Coderch, Miquel F. Segura, Raquel Fueyo, Judit Arguimbau, Erika Zodda, Raquel Bermudo, Immaculada Alonso, Xavier Caparrós, Marta Cascante, Arash Rafii Tabrizi, Yibin Kang, Marian Martínez-Balbás, Stephen J. Weiss, Jerónimo Blanco & 3 others Montserrat Muñoz, Pedro L. Fernández, Timothy M. Thomson

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

MicroRNAs are critical regulators of gene networks in normal and abnormal biological processes. Focusing on invasive ductal breast cancer (IDC), we have found dysregulated expression in tumor samples of several microRNAs, including the miR- 200 family, along progression from primary tumors to distant metastases, further reflected in higher blood levels of miR-200b and miR-7 in IDC patients with regional or distant metastases relative to patients with primary node-negative tumors. Forced expression of miR-200s in MCF10CA1h mammary cells induced an enhanced epithelial program, aldehyde dehydrogenase (ALDH) activity, mammosphere growth and ability to form branched tubuloalveolar structures while promoting orthotopic tumor growth and lung colonization in vivo. MiR-200s also induced the constitutive activation of the PI3K-Akt signaling through downregulation of PTEN, and the enhanced mammosphere growth and ALDH activity induced in MCF10CA1h cells by miR-200s required the activation of this signaling pathway. Interestingly, the morphology of tumors formed in vivo by cells expressing miR-200s was reminiscent of metaplastic breast cancer (MBC). Indeed, the epithelial components of MBC samples expressed significantly higher levels of miR-200s than their mesenchymal components and displayed a marker profile compatible with luminal progenitor cells. We propose that microRNAs of the miR-200 family promote traits of highly proliferative breast luminal progenitor cells, thereby exacerbating the growth and metastatic properties of transformed mammary epithelial cells.

Original languageEnglish
Pages (from-to)83384-83406
Number of pages23
JournalOncotarget
Volume8
Issue number48
DOIs
Publication statusPublished - 1 Jan 2017

Fingerprint

MicroRNAs
Breast
Stem Cells
Breast Neoplasms
Aldehyde Dehydrogenase
Neoplasms
Growth
Neoplasm Metastasis
Biological Phenomena
Aptitude
Gene Regulatory Networks
Regulator Genes
Phosphatidylinositol 3-Kinases
Down-Regulation
Epithelial Cells
Lung

Keywords

  • Epithelial reprogramming
  • Invasive ductal breast cancer
  • MicroRNAs
  • MiR-200
  • Progenitor luminal cells

ASJC Scopus subject areas

  • Oncology

Cite this

Sánchez-Cid, L., Pons, M., Lozano, J. J., Rubio, N., Guerra-Rebollo, M., Soriano, A., ... Thomson, T. M. (2017). MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells. Oncotarget, 8(48), 83384-83406. https://doi.org/10.18632/oncotarget.20698

MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells. / Sánchez-Cid, Lourdes; Pons, Mònica; Lozano, Juan José; Rubio, Nuria; Guerra-Rebollo, Marta; Soriano, Aroa; Paris-Coderch, Laia; Segura, Miquel F.; Fueyo, Raquel; Arguimbau, Judit; Zodda, Erika; Bermudo, Raquel; Alonso, Immaculada; Caparrós, Xavier; Cascante, Marta; Tabrizi, Arash Rafii; Kang, Yibin; Martínez-Balbás, Marian; Weiss, Stephen J.; Blanco, Jerónimo; Muñoz, Montserrat; Fernández, Pedro L.; Thomson, Timothy M.

In: Oncotarget, Vol. 8, No. 48, 01.01.2017, p. 83384-83406.

Research output: Contribution to journalArticle

Sánchez-Cid, L, Pons, M, Lozano, JJ, Rubio, N, Guerra-Rebollo, M, Soriano, A, Paris-Coderch, L, Segura, MF, Fueyo, R, Arguimbau, J, Zodda, E, Bermudo, R, Alonso, I, Caparrós, X, Cascante, M, Tabrizi, AR, Kang, Y, Martínez-Balbás, M, Weiss, SJ, Blanco, J, Muñoz, M, Fernández, PL & Thomson, TM 2017, 'MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells', Oncotarget, vol. 8, no. 48, pp. 83384-83406. https://doi.org/10.18632/oncotarget.20698
Sánchez-Cid L, Pons M, Lozano JJ, Rubio N, Guerra-Rebollo M, Soriano A et al. MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells. Oncotarget. 2017 Jan 1;8(48):83384-83406. https://doi.org/10.18632/oncotarget.20698
Sánchez-Cid, Lourdes ; Pons, Mònica ; Lozano, Juan José ; Rubio, Nuria ; Guerra-Rebollo, Marta ; Soriano, Aroa ; Paris-Coderch, Laia ; Segura, Miquel F. ; Fueyo, Raquel ; Arguimbau, Judit ; Zodda, Erika ; Bermudo, Raquel ; Alonso, Immaculada ; Caparrós, Xavier ; Cascante, Marta ; Tabrizi, Arash Rafii ; Kang, Yibin ; Martínez-Balbás, Marian ; Weiss, Stephen J. ; Blanco, Jerónimo ; Muñoz, Montserrat ; Fernández, Pedro L. ; Thomson, Timothy M. / MicroRNA-200, associated with metastatic breast cancer, promotes traits of mammary luminal progenitor cells. In: Oncotarget. 2017 ; Vol. 8, No. 48. pp. 83384-83406.
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AU - Rubio, Nuria

AU - Guerra-Rebollo, Marta

AU - Soriano, Aroa

AU - Paris-Coderch, Laia

AU - Segura, Miquel F.

AU - Fueyo, Raquel

AU - Arguimbau, Judit

AU - Zodda, Erika

AU - Bermudo, Raquel

AU - Alonso, Immaculada

AU - Caparrós, Xavier

AU - Cascante, Marta

AU - Tabrizi, Arash Rafii

AU - Kang, Yibin

AU - Martínez-Balbás, Marian

AU - Weiss, Stephen J.

AU - Blanco, Jerónimo

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