Cell Reports (Apr 2021)
Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype
- Fátima Valdés-Mora,
- Robert Salomon,
- Brian Stewart Gloss,
- Andrew Man Kit Law,
- Jeron Venhuizen,
- Lesley Castillo,
- Kendelle Joan Murphy,
- Astrid Magenau,
- Michael Papanicolaou,
- Laura Rodriguez de la Fuente,
- Daniel Lee Roden,
- Yolanda Colino-Sanguino,
- Zoya Kikhtyak,
- Nona Farbehi,
- James Ronald William Conway,
- Neblina Sikta,
- Samantha Richelle Oakes,
- Thomas Robert Cox,
- Seán Ignatius O’Donoghue,
- Paul Timpson,
- Christopher John Ormandy,
- David Gallego-Ortega
Affiliations
- Fátima Valdés-Mora
- Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; Personalised Medicine, Children’s Cancer Institute, Sydney, NSW 2031, Australia; St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Garvan-Weizmann Centre for Cellular Genomics. Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; Corresponding author
- Robert Salomon
- Personalised Medicine, Children’s Cancer Institute, Sydney, NSW 2031, Australia; Garvan-Weizmann Centre for Cellular Genomics. Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; Institute for Biomedical Materials and Devices, University of Technology Sydney, Sydney, NSW 2007, Australia
- Brian Stewart Gloss
- St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Andrew Man Kit Law
- St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Jeron Venhuizen
- Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Lesley Castillo
- Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Kendelle Joan Murphy
- St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Astrid Magenau
- Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Michael Papanicolaou
- St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; School of Life Sciences, University of Technology Sydney, Sydney, NSW 2007, Australia
- Laura Rodriguez de la Fuente
- Personalised Medicine, Children’s Cancer Institute, Sydney, NSW 2031, Australia; St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Daniel Lee Roden
- St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Garvan-Weizmann Centre for Cellular Genomics. Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Yolanda Colino-Sanguino
- Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; Personalised Medicine, Children’s Cancer Institute, Sydney, NSW 2031, Australia; St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia
- Zoya Kikhtyak
- Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Nona Farbehi
- Garvan-Weizmann Centre for Cellular Genomics. Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- James Ronald William Conway
- Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Neblina Sikta
- Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Samantha Richelle Oakes
- St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Thomas Robert Cox
- St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Seán Ignatius O’Donoghue
- Genomics and Epigenetics Theme, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; CSIRO Data61, Eveleigh, NSW 2015, Australia; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW 2052, Australia
- Paul Timpson
- St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- Christopher John Ormandy
- St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
- David Gallego-Ortega
- St. Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW 2010, Australia; Garvan-Weizmann Centre for Cellular Genomics. Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; Cancer Theme, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; Corresponding author
- Journal volume & issue
-
Vol. 35,
no. 2
p. 108945
Abstract
Summary: Basal breast cancer is associated with younger age, early relapse, and a high mortality rate. Here, we use unbiased droplet-based single-cell RNA sequencing (RNA-seq) to elucidate the cellular basis of tumor progression during the specification of the basal breast cancer subtype from the luminal progenitor population in the MMTV-PyMT (mouse mammary tumor virus-polyoma middle tumor-antigen) mammary tumor model. We find that basal-like cancer cells resemble the alveolar lineage that is specified upon pregnancy and encompass the acquisition of an aberrant post-lactation developmental program of involution that triggers remodeling of the tumor microenvironment and metastatic dissemination. This involution mimicry is characterized by a highly interactive multicellular network, with involution cancer-associated fibroblasts playing a pivotal role in extracellular matrix remodeling and immunosuppression. Our results may partially explain the increased risk and poor prognosis of breast cancer associated with childbirth.
