Cell Reports (Jul 2021)
SMAD4 represses FOSL1 expression and pancreatic cancer metastatic colonization
- Chao Dai,
- Jonathan P. Rennhack,
- Taylor E. Arnoff,
- Maneesha Thaker,
- Scott T. Younger,
- John G. Doench,
- August Yue Huang,
- Annan Yang,
- Andrew J. Aguirre,
- Belinda Wang,
- Evan Mun,
- Joyce T. O’Connell,
- Ying Huang,
- Katherine Labella,
- Jessica A. Talamas,
- Ji Li,
- Nina Ilic,
- Justin Hwang,
- Andrew L. Hong,
- Andrew O. Giacomelli,
- Ole Gjoerup,
- David E. Root,
- William C. Hahn
Affiliations
- Chao Dai
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Jonathan P. Rennhack
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Taylor E. Arnoff
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Maneesha Thaker
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Scott T. Younger
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- John G. Doench
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- August Yue Huang
- Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA 02115, USA
- Annan Yang
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Andrew J. Aguirre
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Belinda Wang
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Evan Mun
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Northeastern University, Boston, MA 02115, USA
- Joyce T. O’Connell
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Ying Huang
- Molecular Pathology Core Lab, Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
- Katherine Labella
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Jessica A. Talamas
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Ji Li
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Nina Ilic
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- Justin Hwang
- Masonic Cancer Center and Department of Medicine, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA
- Andrew L. Hong
- Department of Pediatrics, Emory University, Atlanta, GA 30322, USA
- Andrew O. Giacomelli
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada
- Ole Gjoerup
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- David E. Root
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
- William C. Hahn
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Corresponding author
- Journal volume & issue
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Vol. 36,
no. 4
p. 109443
Abstract
Summary: Metastasis is a complex and poorly understood process. In pancreatic cancer, loss of the transforming growth factor (TGF)-β/BMP effector SMAD4 is correlated with changes in altered histopathological transitions, metastatic disease, and poor prognosis. In this study, we use isogenic cancer cell lines to identify SMAD4 regulated genes that contribute to the development of metastatic colonization. We perform an in vivo screen identifying FOSL1 as both a SMAD4 target and sufficient to drive colonization to the lung. The targeting of these genes early in treatment may provide a therapeutic benefit.
