ArticleNature communications2018
Targeting SPINK1 in the damaged tumour microenvironment alleviates therapeutic resistance.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 126 citations in OpenAlex.
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- SPINK1-driven cellular heterogeneity and interaction networks in intrahepatic cholangiocarcinoma revealed by integrated multi-omics analysis.Journal of advanced research · 2026Article
- Large-scale proteomics in early pregnancy and timing of onset of hypertensive disorders of pregnancy.medRxiv : the preprint server for health sciences · 2026Article
- Senescent endothelial cell-derived extracellular vesicles promote neoadjuvant chemoresistance in colorectal cancer via GPX4.Communications biology · 2026Article
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- The natural flavonoid dihydromyricetin targets senescent cells via PRDX2 and alleviates age-related diseases.Nature communications · 2026Article
- Expression of Antioxidant Defense Genes Determines Synergistic Ferroptosis Induction by the Combination of Erastin and Omega-3 Docosahexaenoic Acid in Prostate Cancer Cells.Doklady. Biochemistry and biophysics · 2026Article
- Biomarkers for Recurrence and Prognosis in Metastatic Urothelial Cancer: Emerging Clinical Applications.Journal of Cancer · 2026Review
- KDM4 Orchestrates Epigenomic Remodeling of Senescent Cells and Potentiates the Senescence-Associated Secretory Phenotype.Aging cell · 2025Article
- Pyrroloquinoline Quinone Is an Effective Senomorphic Agent to Target the Pro-Inflammatory Phenotype of Senescent Cells.Aging cell · 2025Article
- Integrated molecular and clinical characterization of pulmonary large cell neuroendocrine carcinoma.Nature communications · 2025Article
- The SPINK Protein Family in Cancer: Emerging Roles in Tumor Progression, Therapeutic Resistance, and Precision Oncology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Exploratory Study of Prognostic Plasma Biomarkers in Patients with Pulmonary Arterial Hypertension.The American journal of pathology · 2025Article
- Review
- Targeting Senescence with Apigenin Improves Chemotherapeutic Efficacy and Ameliorates Age-Related Conditions in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Patient-Derived Bladder Cancer Organoids as a Valuable Tool for Understanding Tumor Biology and Developing Personalized Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Regulation of Cellular Senescence in Cancer.Biomolecules · 2025Review
- Senescence-associated secretory phenotype in lung cancer: remodeling the tumor microenvironment for metastasis and immune suppression.Frontiers in oncology · 2025Review
- Inhibition of SIRT3 by a specific inhibitor induces cellular senescence and growth arrest of ovarian granulosa cell tumor via p53 and NF-κB axis.Frontiers in pharmacology · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 10 institutions in 3 countries.
Funding
Abstract
Chemotherapy and radiation not only trigger cancer cell apoptosis but also damage stromal cells in the tumour microenvironment (TME), inducing a senescence-associated secretory phenotype (SASP) characterized by chronic secretion of diverse soluble factors. Here we report serine protease inhibitor Kazal type I (SPINK1), a SASP factor produced in human stromal cells after genotoxic treatment. DNA damage causes SPINK1 expression by engaging NF-κB and C/EBP, while paracrine SPINK1 promotes cancer cell aggressiveness particularly chemoresistance. Strikingly, SPINK1 reprograms the expression profile of cancer cells, causing prominent epithelial-endothelial transition (EET), a phenotypic switch mediated by EGFR signaling but hitherto rarely reported for a SASP factor. In vivo, SPINK1 is expressed in the stroma of solid tumours and is routinely detectable in peripheral blood of cancer patients after chemotherapy. Our study substantiates SPINK1 as both a targetable SASP factor and a novel noninvasive biomarker of therapeutically damaged TME for disease control and clinical surveillance.
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