Nature Communications (Oct 2022)
BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking clusterin expression in cancer associated fibroblasts with HSF1 signaling
- Lee Shaashua,
- Aviad Ben-Shmuel,
- Meirav Pevsner-Fischer,
- Gil Friedman,
- Oshrat Levi-Galibov,
- Subhiksha Nandakumar,
- Debra Barki,
- Reinat Nevo,
- Lauren E. Brown,
- Wenhan Zhang,
- Yaniv Stein,
- Chen Lior,
- Han Sang Kim,
- Linda Bojmar,
- William R. Jarnagin,
- Nicolas Lecomte,
- Shimrit Mayer,
- Roni Stok,
- Hend Bishara,
- Rawand Hamodi,
- Ephrat Levy-Lahad,
- Talia Golan,
- John A. Porco,
- Christine A. Iacobuzio-Donahue,
- Nikolaus Schultz,
- David A. Tuveson,
- David Lyden,
- David Kelsen,
- Ruth Scherz-Shouval
Affiliations
- Lee Shaashua
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Aviad Ben-Shmuel
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Meirav Pevsner-Fischer
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Gil Friedman
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Oshrat Levi-Galibov
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Subhiksha Nandakumar
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
- Debra Barki
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Reinat Nevo
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Lauren E. Brown
- Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University
- Wenhan Zhang
- Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University
- Yaniv Stein
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Chen Lior
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Han Sang Kim
- Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine
- Linda Bojmar
- Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine
- William R. Jarnagin
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center
- Nicolas Lecomte
- David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center
- Shimrit Mayer
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Roni Stok
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Hend Bishara
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Rawand Hamodi
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- Ephrat Levy-Lahad
- The Fuld Family Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Faculty of Medicine, The Hebrew University of Jerusalem
- Talia Golan
- Oncology Institute, Sheba Medical Center at Tel-Hashomer, Tel Aviv University
- John A. Porco
- Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University
- Christine A. Iacobuzio-Donahue
- David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center
- Nikolaus Schultz
- Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
- David A. Tuveson
- Cancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor
- David Lyden
- Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medicine
- David Kelsen
- Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College
- Ruth Scherz-Shouval
- Department of Biomolecular Sciences, The Weizmann Institute of Science
- DOI
- https://doi.org/10.1038/s41467-022-34081-3
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 21
Abstract
Cancer-associated fibroblasts are transcriptionally rewired by signals from the cancer cells, resulting in heterogeneous populations. Here the authors show that loss of BRCA function in pancreatic cancer cells leads to HSF1–dependent accumulation of immune-regulatory clusterin-positive cancer associated fibroblasts.
