Research ArticleCANCER
Increased lysosomal biomass is responsible for the resistance of triple-negative breast cancers to CDK4/6 inhibition
- View ORCID ProfileAnne Fassl1,2,
- Christopher Brain3,
- Monther Abu-Remaileh4,5,6,
- Iga Stukan1,
- Deborah Butter1,
- Piotr Stepien1,
- Avery S. Feit7,8,
- Johann Bergholz1,9,
- Wojciech Michowski1,2,
- Tobias Otto1,2,
- View ORCID ProfileQing Sheng3,
- Alice Loo3,
- Walter Michael3,
- Ralph Tiedt10,
- Carmine DeAngelis11,12,13,
- View ORCID ProfileRachel Schiff11,12,
- View ORCID ProfileBaishan Jiang1,9,
- View ORCID ProfileBojana Jovanovic7,8,
- View ORCID ProfileKarolina Nowak1,
- View ORCID ProfileMaria Ericsson14,
- View ORCID ProfileMichael Cameron15,
- View ORCID ProfileNathanael Gray1,9,
- Deborah Dillon16,
- Jean J. Zhao1,9,17,
- View ORCID ProfileDavid M. Sabatini4,17,18,19,
- View ORCID ProfileRinath Jeselsohn7,8,
- Myles Brown7,8,
- View ORCID ProfileKornelia Polyak7,8,* and
- View ORCID ProfilePiotr Sicinski1,2,*
- 1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
- 2Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
- 3Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
- 4Whitehead Institutes for Biomedical Research and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
- 5Departments of Chemical Engineering and Genetics, Stanford University, Stanford, CA 94305, USA.
- 6Institute for Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, 290 Jane Stanford Way, Stanford, CA 94305, USA.
- 7Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
- 8Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.
- 9Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
- 10Novartis Institutes for Biomedical Research, Oncology Disease Area, 4057 Basel, Switzerland.
- 11Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
- 12Department of Medicine and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
- 13Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
- 14Electron Microscopy Facility, Harvard Medical School, Boston, MA 02115, USA.
- 15Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458, USA.
- 16Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
- 17Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
- 18Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
- 19Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
- ↵*Corresponding author. Email: kornelia_polyak{at}dfci.harvard.edu (K.P.); peter_sicinski{at}dfci.harvard.edu (P.S.)
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Science Advances 17 Jun 2020:
Vol. 6, no. 25, eabb2210
DOI: 10.1126/sciadv.abb2210
Vol. 6, no. 25, eabb2210
DOI: 10.1126/sciadv.abb2210
Anne Fassl
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
2Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Christopher Brain
3Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Monther Abu-Remaileh
4Whitehead Institutes for Biomedical Research and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
5Departments of Chemical Engineering and Genetics, Stanford University, Stanford, CA 94305, USA.
6Institute for Chemistry, Engineering and Medicine for Human Health (ChEM-H), Stanford University, 290 Jane Stanford Way, Stanford, CA 94305, USA.
Iga Stukan
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Deborah Butter
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Piotr Stepien
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Avery S. Feit
7Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
8Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.
Johann Bergholz
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
9Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Wojciech Michowski
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
2Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Tobias Otto
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
2Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Qing Sheng
3Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Alice Loo
3Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Walter Michael
3Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Ralph Tiedt
10Novartis Institutes for Biomedical Research, Oncology Disease Area, 4057 Basel, Switzerland.
Carmine DeAngelis
11Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
12Department of Medicine and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
13Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.
Rachel Schiff
11Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
12Department of Medicine and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Baishan Jiang
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
9Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Bojana Jovanovic
7Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
8Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.
Karolina Nowak
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Maria Ericsson
14Electron Microscopy Facility, Harvard Medical School, Boston, MA 02115, USA.
Michael Cameron
15Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458, USA.
Nathanael Gray
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
9Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Deborah Dillon
16Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Jean J. Zhao
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
9Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
17Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
David M. Sabatini
4Whitehead Institutes for Biomedical Research and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
17Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
18Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
19Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Rinath Jeselsohn
7Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
8Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.
Myles Brown
7Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
8Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.
Kornelia Polyak
7Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
8Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.
Piotr Sicinski
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
2Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
