title: Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts.
abstract: Previous studies have suggested that breast cancer stem cells (BCSCs) mediate metastasis, are resistant to radiation and chemotherapy, and contribute to relapse. Although several BCSC markers have been described, it is unclear whether these markers identify the same or independent BCSCs. Here, we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition [EMT]) and epithelial-like (mesenchymal-epithelial transition [MET]) states. Mesenchymal-like BCSCs characterized as CD24(-)CD44(+) are primarily quiescent and localized at the tumor invasive front, whereas epithelial-like BCSCs express aldehyde dehydrogenase (ALDH), are proliferative, and are located more centrally. The gene-expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across different molecular subtypes of breast cancer, and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs that allows them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion, dissemination, and growth at metastatic sites.
authors: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
authors: Suling
authors: S
authors: Liu
authors: Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors: Yang
authors: Y
authors: Cong
authors: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
authors: Dong
authors: D
authors: Wang
authors: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
authors: Yu
authors: Y
authors: Sun
authors: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People's Republic of China.
authors: Lu
authors: L
authors: Deng
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Yajing
authors: Y
authors: Liu
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Rachel
authors: R
authors: Martin-Trevino
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Li
authors: L
authors: Shang
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Sean P
authors: SP
authors: McDermott
authors: Methodist Cancer Center, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors: Melissa D
authors: MD
authors: Landis
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Suhyung
authors: S
authors: Hong
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: April
authors: A
authors: Adams
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Rosemarie
authors: R
authors: D'Angelo
authors: Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, UMR891 INSERM/Institut Paoli-Calmettes, Université de la Méditerranée, Marseille 13273, France.
authors: Christophe
authors: C
authors: Ginestier
authors: Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, UMR891 INSERM/Institut Paoli-Calmettes, Université de la Méditerranée, Marseille 13273, France.
authors: Emmanuelle
authors: E
authors: Charafe-Jauffret
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Shawn G
authors: SG
authors: Clouthier
authors: Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire, UMR891 INSERM/Institut Paoli-Calmettes, Université de la Méditerranée, Marseille 13273, France.
authors: Daniel
authors: D
authors: Birnbaum
authors: Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors: Stephen T
authors: ST
authors: Wong
authors: Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors: Ming
authors: M
authors: Zhan
authors: Methodist Cancer Center, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors: Jenny C
authors: JC
authors: Chang
authors: Comprehensive Cancer Center, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Max S
authors: MS
authors: Wicha
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D051927:CD24 Antigen / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D051927:CD24 Antigen; D018960:Hyaluronan Receptors; D000444:Aldehyde Dehydrogenase