Integrin-β4 identifies cancer stem cell-enriched populations of partially mesenchymal carcinoma cells
Abstract
It is widely appreciated that carcinoma cells exhibiting certain mesenchymal traits are enriched for cancer stem cells (CSCs) and can give rise to tumors with aggressive features. Whereas it has been proposed that mesenchymal carcinoma cell populations are internally heterogeneous, the field has made little progress in resolving the specific subtypes of mesenchymal carcinoma cells that pose the greatest risk for patients. We demonstrate the utility of integrin-β4 (ITGB4) in segregating these cells into distinct subpopulations with differing tumor-initiating abilities and pathological behaviors. In addition, we identified mechanistic links between ZEB1 (zinc finger E-box binding homeobox 1) and TAp63α (tumor protein 63 isoform 1) as regulators of ITGB4 expression and demonstrate that ITGB4 can be used as a marker to determine which patients are more likely to relapse after treatment.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 07, 2017
- Source ID
- 10.1073/pnas.1618298114
Entities
People
- Brian Bierie
- Christine L. Chaffer
- Cornelia Kroeger
- Daniel G. Stover
- Diwakar R. Pattabiraman
- Ferenc Reinhardt
- Joana Liu Donaher
- Prathapan Thiru
- Robert Weinberg
- Sarah E Pierce
- Zuzana Keckesova
Organizations
- Brown University
- Congressionally Directed Medical Research Programs
- Dana–Farber Cancer Institute
- Massachusetts Institute of Technology
- National Cancer Institute
- National Health and Medical Research Council
- Whitehead Institute