ArticleCell reports2021
Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity.
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Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24citing papers in PubMed
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Metabolic reprogramming in cancer-associated fibroblasts: orchestrating the tumor immune microenvironment and response to immune checkpoint blockade.Experimental hematology & oncology · 2026Review
- Cellular architecture and neighborhood-informed virtual spatial tumor profiling from histopathology.Cell · 2026Article
- Identification, functional insights and therapeutic targeting of EMT tumour states.Nature reviews. Cancer · 2026Review
- The role of MiRNA-mediated tumor microenvironment in bone metastasis from a multi-omics perspective: cross-cancer mechanisms and clinical translation.Frontiers in oncology · 2026Review
- Cancer-associated fibroblast heterogeneity and its role in reshaping immunotherapy in solid cancers: potential strategies and clinical promise.Frontiers in cell and developmental biology · 2026Review
- Plasticity and Functional Heterogeneity of Cancer-Associated Fibroblasts.Cancer research · 2025Review
- Interleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC).Journal of translational medicine · 2025Article
- Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells.The Journal of clinical investigation · 2025Article
- Cancer-Associated Fibroblasts as the "Architect" of the Lung Cancer Immune Microenvironment: Multidimensional Roles and Synergistic Regulation with Radiotherapy.International journal of molecular sciences · 2025Review
- The extracellular matrix protein type I collagen and fibronectin are regulated by β-arrestin-1/endothelin axis in human ovarian fibroblasts.Journal of experimental & clinical cancer research : CR · 2025Article
- miR-224 activates cancer-associated fibroblasts to enhance lung cancer cell migration and invasion by targeting Akirin1.Scientific reports · 2025Article
- The role of transcription factors in the crosstalk between cancer-associated fibroblasts and tumor cells.Journal of advanced research · 2025Review
- Integration of single-cell transcriptome and chromatin accessibility and its application on tumor investigation.Life medicine · 2024Review
- Distinct fibroblast subpopulations associated with bone, brain or intrapulmonary metastasis in advanced non-small-cell lung cancer.Clinical and translational medicine · 2024Article
- Transcription factors in fibroblast plasticity and CAF heterogeneity.Journal of experimental & clinical cancer research : CR · 2023Review
- Cancer-associated fibroblasts in papillary thyroid carcinoma.Clinical and experimental medicine · 2023Article
- EMT-activated secretory and endocytic vesicular trafficking programs underlie a vulnerability to PI4K2A antagonism in lung cancer.The Journal of clinical investigation · 2023Article
- From the Catastrophic Objective Irreproducibility of Cancer Research and Unavoidable Failures of Molecular Targeted Therapies to the Sparkling Hope of Supramolecular Targeted Strategies.International journal of molecular sciences · 2023Review
- Metastasis and cancer associated fibroblasts: taking it up a NOTCH.Frontiers in cell and developmental biology · 2023Review
- Review
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Authors and funding
34 authors at 8 institutions in 2 countries.
Neus Bota-RabassedasDepartments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Priyam BanerjeeDepartments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yichi NiuDepartments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Wenjian CaoDepartments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Jiayi LuoDepartments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Yuanxin XiBioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xiaochao TanDepartments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Kuanwei ShengDepartments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Young-Ho AhnDepartment of Molecular Medicine and Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea.
Sieun LeeDepartment of Molecular Medicine and Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea.
Edwin Roger ParraTranslational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jaime Rodriguez-CanalesTranslational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jacob AlbrittonDepartment of Molecular Medicine and Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans University, Seoul 07804, Korea.
Michael WeigerGenitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xin LiuDepartments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hou-Fu GuoDepartments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jiang YuDepartments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
B Leticia RodriguezDepartments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Joshua J A FirestoneHouston, TX, USA.
Barbara MinoTranslational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Chad J CreightonDan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
Luisa M SolisTranslational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Pamela VillalobosTranslational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Maria Gabriela RasoTranslational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Daniel W SazerDepartment of Bioengineering, Rice University, Houston, TX, USA.
Don L GibbonsDepartments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
William K RussellDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
Gregory D LongmoreDepartment 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 WistubaTranslational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jing WangBioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Harold A ChapmanDepartment of Medicine, University of California, San Francisco Cardiovascular Research Institute, San Francisco, CA, USA.
Jordan S MillerDepartment of Bioengineering, Rice University, Houston, TX, USA. Electronic address: jmil@rice.edu.
Chenghang ZongDepartments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. Electronic address: chenghang.zong@bcm.edu.
Jonathan M KurieDepartments of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jkurie@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USBaylor College of Medicine · USEwha Womans University · KRRice University · USThe University of Texas Medical Branch at Galveston · USUniversity of California, San Francisco · USUniversity of Houston · USWashington University in St. Louis · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MTumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9MUNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI GIBBONS, DON LYNN · 1996 to 2024
$57.4MRegulation of lung cancer growth and metastasis by an actionable driver of vesicle biogenesis in the GolgiR01CA236781 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KURIE, JONATHAN M · 2020 to 2024
$2.2MTumor stromal effects of DDR2 in metastasis regulationR01CA223758 · NCI · WASHINGTON UNIVERSITY · PI LONGMORE, GREGORY D. · 2018 to 2022
$1.9MRegulation of lung cancer metastasis through transcriptional control of the Golgi apparatusR01CA211125 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KURIE, JONATHAN M · 2017 to 2021
$1.8MNOVEL SMALL MOLECULE INHIBITION OF DDR2 TO PREVENT BREAST CANCER METASTASISR01CA196205 · NCI · WASHINGTON UNIVERSITY · PI LONGMORE, GREGORY D. · 2015 to 2019
$1.7MRegulation of Lung Cancer Metastasis by ZEB1R01CA181184 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KURIE, JONATHAN M · 2014 to 2018
$1.7MDetermining structural features of a collagen lysyl hydroxylase that promotes lung cancer metastasisR00CA225633 · NCI · UNIVERSITY OF KENTUCKY · PI GUO, HOUFU · 2020 to 2022
$730kBD Biosciences Special Order LSRIIS10RR024574 · NCRR · BAYLOR COLLEGE OF MEDICINE · PI LUMPKIN, ELLEN A · 2009 to 2009
$430kDetermining structural features of a collagen lysyl hydroxylase that promotes lung cancer metastasisK99CA225633 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GUO, HOUFU · 2018 to 2019
$224kNCI NIH HHS K99 CA225633NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA125123NCI NIH HHS P50 CA070907NCI NIH HHS R00 CA225633NCI NIH HHS R01 CA181184NCI NIH HHS R01 CA196205NCI NIH HHS R01 CA211125NCI NIH HHS R01 CA223758NCI NIH HHS R01 CA236781NCRR NIH HHS S10 RR024574
Abstract
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.
Indexed as
Adenocarcinoma of LungAlpha-GlobulinsAnimalsCancer-Associated FibroblastsCell CommunicationCell Line, TumorCell MovementCell ProliferationDiscoidin Domain Receptor 2Epithelial CellsEpithelial-Mesenchymal TransitionGene Expression ProfilingGene Expression Regulation, NeoplasticHumansKidney NeoplasmsLung NeoplasmsAlpha-GlobulinsDDR2 protein, humanDiscoidin Domain Receptor 2inter-alpha-inhibitorZEB1 protein, humanZinc Finger E-box-Binding Homeobox 1cancer-associated fibroblastEMTinvasionlung cancermetastasismicroRNAsecretionsingle-cell RNA sequencingtumor microenvironment
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