Cell Reports (Apr 2021)
Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity
- Neus Bota-Rabassedas,
- Priyam Banerjee,
- Yichi Niu,
- Wenjian Cao,
- Jiayi Luo,
- Yuanxin Xi,
- Xiaochao Tan,
- Kuanwei Sheng,
- Young-Ho Ahn,
- Sieun Lee,
- Edwin Roger Parra,
- Jaime Rodriguez-Canales,
- Jacob Albritton,
- Michael Weiger,
- Xin Liu,
- Hou-Fu Guo,
- Jiang Yu,
- B. Leticia Rodriguez,
- Joshua J.A. Firestone,
- Barbara Mino,
- Chad J. Creighton,
- Luisa M. Solis,
- Pamela Villalobos,
- Maria Gabriela Raso,
- Daniel W. Sazer,
- Don L. Gibbons,
- William K. Russell,
- Gregory D. Longmore,
- Ignacio I. Wistuba,
- Jing Wang,
- Harold A. Chapman,
- Jordan S. Miller,
- Chenghang Zong,
- Jonathan M. Kurie
Affiliations
- Neus Bota-Rabassedas
- Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Priyam Banerjee
- Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Yichi Niu
- Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
- Wenjian Cao
- Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
- Jiayi Luo
- Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
- Yuanxin Xi
- Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Xiaochao Tan
- Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Kuanwei Sheng
- Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
- Young-Ho Ahn
- Department of Molecular Medicine and Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea
- Sieun Lee
- Department of Molecular Medicine and Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea
- Edwin Roger Parra
- Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Jaime Rodriguez-Canales
- Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Jacob Albritton
- Department of Molecular Medicine and Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea
- Michael Weiger
- Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Xin Liu
- Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Hou-Fu Guo
- Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Jiang Yu
- Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- B. Leticia Rodriguez
- Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Joshua J.A. Firestone
- Houston, TX, USA
- Barbara Mino
- Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Chad J. Creighton
- Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA
- Luisa M. Solis
- Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Pamela Villalobos
- Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Maria Gabriela Raso
- Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Daniel W. Sazer
- Department of Bioengineering, Rice University, Houston, TX, USA
- Don L. Gibbons
- Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- William K. Russell
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
- Gregory D. Longmore
- Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA; Department of Cell Biology & Physiology, Washington University in St. Louis, St. Louis, MO, USA
- Ignacio I. Wistuba
- Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Jing Wang
- Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Harold A. Chapman
- Department of Medicine, University of California, San Francisco Cardiovascular Research Institute, San Francisco, CA, USA
- Jordan S. Miller
- Department of Bioengineering, Rice University, Houston, TX, USA; Corresponding author
- Chenghang Zong
- Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Corresponding author
- Jonathan M. Kurie
- Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Corresponding author
- Journal volume & issue
-
Vol. 35,
no. 3
p. 109009
Abstract
Summary: Cancer cells function as primary architects of the tumor microenvironment. However, the molecular features of cancer cells that govern stromal cell phenotypes remain unclear. Here, we show that cancer-associated fibroblast (CAF) heterogeneity is driven by lung adenocarcinoma (LUAD) cells at either end of the epithelial-to-mesenchymal transition (EMT) spectrum. LUAD cells that have high expression of the EMT-activating transcription factor ZEB1 reprogram CAFs through a ZEB1-dependent secretory program and direct CAFs to the tips of invasive projections through a ZEB1-driven CAF repulsion process. The EMT, in turn, sensitizes LUAD cells to pro-metastatic signals from CAFs. Thus, CAFs respond to contextual cues from LUAD cells to promote metastasis.
