ArticleCancer discovery2014
p38MAPK plays a crucial role in stromal-mediated tumorigenesis.
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In one paragraph
Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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0cells of the map it votes in
115citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 3% of its field
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 167 citations in OpenAlex.
- Broad repression of DNA repair genes in senescent cells identified by integration of transcriptomic data.Nucleic acids research · 2025Pooled it
- SenFlag gene signature identifies senescent cells in mouse and human tissues through a conserved core transcriptional program.The EMBO journal · 2026Article
- Beyond biochemical cascades: novel bio-mechanical and epigenetic paradigms of glial SASP in brain aging.Metabolic brain disease · 2026Review
- T Cell Immunosenescence in Inflammatory Skin Diseases: Pathogenesis and Therapeutic Targets.Aging cell · 2026Review
- Targeting p38α in cancer: challenges, opportunities, and emerging strategies.Molecular oncology · 2026Review
- Natural Products as Anti-Senescence-Associated Secretory Phenotype (SASP) Agents.Current medicinal chemistry · 2026Review
- Chemotherapy-induced adipo-lineage cell senescence drives bone loss.Nature communications · 2025Article
- The controversial role of senescence-associated secretory phenotype (SASP) in cancer therapy.Molecular cancer · 2025Review
- Stromal senescence contributes to age-related increases in cancer.Nature reviews. Cancer · 2025Review
- Strain Promotes Triple Negative Breast Cancer Proliferation and Migration Via VEGFR-2.Cellular and molecular bioengineering · 2025Article
- Difference Analysis of MiRNA Expression Profiles in Aged Female Rat Adipose Tissue Regulated by HIIT and MICT.Cell biochemistry and biophysics · 2025Article
- Immunosenescence and cancer: molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges.Journal of hematology & oncology · 2025Review
- Molecular Regulation of SASP in Cellular Senescence: Therapeutic Implications and Translational Challenges.Cells · 2025Review
- A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions.Nature aging · 2025Article
- A machine learning approach identifies cellular senescence on transcriptome data of human cells in vitro.GeroScience · 2025Article
- New Insights into the Role of Cellular Senescence and Its Therapeutic Implications in Ocular Diseases.Bioengineering (Basel, Switzerland) · 2025Review
- Senescent macrophages in cancer: roles in tumor progression and treatment opportunities.Cancer biology & medicine · 2025Review
- Osteosarcoma Exosome Priming of Primary Human Lung Fibroblasts Induces an Immune Modulatory and Protumorigenic Phenotype.Cancer research communications · 2025Article
- Cellular senescence offers distinct immunological vulnerabilities in cancer.Trends in cancer · 2025Review
- Cellular senescence: mechanisms and relevance to cancer and aging.Journal of biochemistry · 2025Review
55 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 2 countries.
Elise AlspachAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TexasAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Kevin C FlanaganAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TexasAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Xianmin LuoAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TexasAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Megan K RuhlandAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TexasAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Hui HuangAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TexasAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Ermira PazolliAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Maureen J DonlinAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TexasAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Timothy MarshAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
David Piwnica-WormsAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Joseph MonahanAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Deborah V NovackAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TexasAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sandra S McAllisterAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TexasAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sheila A StewartAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TexasAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TexasAuthors' Affiliations: Departments of Cell Biology and Physiology, Medicine, and Pathology and Immunology; BRIGHT Institute, Washington University School of Medicine; Departments of Biochemistry & Molecular Biology and Molecular Microbiology & Immunology, Saint Louis University School of Medicine; Confluence Life Sciences, Inc., St. Louis, Missouri; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston; Harvard Stem Cell Institute and Broad Institute of Harvard and MIT, Cambridge, Massachusetts; and Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas sheila.stewart@wust
Brigham and Women's Hospital · USBroad Institute · USSaint Louis University · USConfluence Life Sciences (United States) · USHarvard University · US
Funding
Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0MWashington University Institute of Clinical and Translational Sciences (UL1)UL1RR024992 · NCRR · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2007 to 2011
$45.4MWU-MDACC Inter-Institutional Molecular Imaging CenterP50CA094056 · NCI · WASHINGTON UNIVERSITY · PI KOPAN, RAPHAEL · 2002 to 2016
$26.3MTRAINING PROGRAM IN CELLULAR AND MOLECULAR BIOLOGYT32GM007067 · NIGMS · WASHINGTON UNIVERSITY · PI TRUE-KROB, HEATHER L · 1985 to 2020
$20.4MThe Role of the Osteoblast Secretome in Bone FormationP30AR057235 · NIAMS · WASHINGTON UNIVERSITY · PI SILVA, MATTHEW J · 2009 to 2018
$5.7MMOLECULAR ONCOLOGY TRAINING GRANTT32CA113275 · NCI · WASHINGTON UNIVERSITY · PI Matthew J Walter · 2006 to 2026
$5.7MUnderstanding How Breast Cancers Activate and Respond to the Systemic EnvironmentR01CA166284 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI MCALLISTER, SANDRA S · 2012 to 2018
$2.2MTHE ROLE OF FIBROBLAST-DERIVED OSTEOPONTIN IN TUMORIGENESISR01CA130919 · NCI · WASHINGTON UNIVERSITY · PI STEWART, SHEILA A · 2009 to 2013
$1.2MNCI NIH HHS 5 R01 CA130919NCI NIH HHS P30 CA091842NCI NIH HHS P50 CA094056NCI NIH HHS P50 CA94056NCI NIH HHS R01 CA130919NCI NIH HHS R01 CA166284NCI NIH HHS R01 CA166284-01NCI NIH HHS T32 CA113275NCRR NIH HHS UL1 RR024992NIAMS NIH HHS P30 AR057235NIGMS NIH HHS T32 GM007067
Abstract
unlabelledNeoplastic cells rely on the tumor microenvironment (TME) for survival and progression factors. Indeed, senescent and cancer-associated fibroblasts (CAF) express factors that promote tumorigenesis that are collectively referred to as the senescence-associated secretory phenotype (SASP). Despite their importance in tumorigenesis, the mechanisms that control TME-derived factor expression remain poorly understood. Here, we address a key unanswered question: how the SASP is sustained in senescent fibroblasts and CAFs. We find that the mitogen-activated protein kinase p38 (p38MAPK) controls AUF1 occupancy on SASP mRNAs and thus controls their stability. The importance of this regulatory mechanism is underscored by our findings that stromal-specific p38MAPK inhibition abrogates the tumor-promoting activities of CAFs and senescent fibroblasts. Our data suggest that targeting SASP mRNA stability through inhibition of p38MAPK will significantly aid the development of clinical strategies to target the TME. SIGNIFICANCE: The TME plays a key role in tumorigenesis. We demonstrate that p38MAPK governs a posttranscriptional mechanism that sustains the protumorigenic SASP. Inhibition of p38MAPK abrogates the tumor-promoting activities of CAFs and senescent fibroblasts. Thus, p38MAPK is a TME-specific Achilles' heel that may be exploited as a new therapeutic target.
Indexed as
Tumor MicroenvironmentAnimalsCell LineCells, CulturedCellular SenescenceFemaleFibroblastsHeterogeneous-Nuclear Ribonucleoprotein DHeterogeneous Nuclear Ribonucleoprotein D0HumansImidazolesLipopolysaccharidesMice, NudeNeoplasmsp38 Mitogen-Activated Protein KinasesProtein Kinase InhibitorsHeterogeneous-Nuclear Ribonucleoprotein DHeterogeneous Nuclear Ribonucleoprotein D0HNRNPD protein, humanHnrpd protein, mouseImidazolesLipopolysaccharidesp38 Mitogen-Activated Protein KinasesProtein Kinase InhibitorsPyridinesSB 203580Tumor Necrosis Factor-alpha
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