ArticleProceedings of the National Academy of Sciences of the United States of America2021
Interplay between desmoglein2 and hypoxia controls metastasis in breast cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Pooled it
- DSG2+ Cancer Stem Cells Co-Located With FAP+ Myofibroblasts in the Tumor Boundary That Determines the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CAFs-derived LAM332 promotes CTCs formation and survival via ITGA3 and contributes to the metastasis of pancreatic ductal adenocarcinoma.Cell death & disease · 2026Article
- DSG2-Directed CAR-T Cells Safely and Universally Eliminate Solid Tumors.Research square · 2026Article
- Extracellular matrix mediates circulating tumor cell clustering in triple-negative breast cancer metastasis.Nature communications · 2026Article
- Tissue-Derived Extracellular Vesicles Define Diagnostic Biomarkers for Renal Cell Carcinoma.Journal of extracellular vesicles · 2026Article
- Desmoglein 2 (DSG2)-knockout human respiratory epithelial cell model to study species B adenovirus receptor usage.Virologica Sinica · 2026Article
- Hirudin suppresses hematogenous metastasis by targeting desmosome junction transition in circulating tumor cell clusters via HIF-1α-DSG2 signaling.Experimental & molecular medicine · 2025Article
- Preliminary investigation of the association between desmoglein-2 expression and patient prognosis following radical surgery for colon cancer.International journal of colorectal disease · 2025Article
- Prediction of Lung Cancer Metastasis Risk Based on Single-Cell Metabolic Profiling of Circulating Tumor Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Collective migration modes in development, tissue repair and cancer.Nature reviews. Molecular cell biology · 2025Review
- Empowering hypoxia to convert cold tumors into hot tumors for breast cancer immunotherapy.Cell death discovery · 2025Review
- Lactylation modification of HIF-1α enhances its stability by blocking VHL recognition.Cell communication and signaling : CCS · 2025Article
- HIF-1α-Mediated Disruption of Cellular Junctions: The Impact of Hypoxia on the Tumor Microenvironment and Invasion.International journal of molecular sciences · 2025Review
- Protrusion force and cell-cell adhesion-induced polarity alignment govern collective migration modes.Biophysical journal · 2025Article
- An energy metabolism-related signature relevant to the tumor immune microenvironment in HNSCC.Discover oncology · 2025Article
- P4HA1 Mediates Hypoxia-Induced Invasion in Human Pancreatic Cancer Organoids.Cancer research communications · 2025Article
- Tumour hypoxia in driving genomic instability and tumour evolution.Nature reviews. Cancer · 2025Review
- Molecular mechanisms and signaling pathways related to brain metastasis in breast cancer.Frontiers in pharmacology · 2025Review
- Yiai Fuzheng decoction inhibits triple-negative breast cancer by remodeling the immune microenvironment.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metastasis is the major cause of cancer death. An increased level of circulating tumor cells (CTCs), metastatic cancer cells that have intravasated into the circulatory system, is particularly associated with colonization of distant organs and poor prognosis. However, the key factors required for tumor cell dissemination and colonization remain elusive. We found that high expression of desmoglein2 (DSG2), a component of desmosome-mediated intercellular adhesion complexes, promoted tumor growth, increased the prevalence of CTC clusters, and facilitated distant organ colonization. The dynamic regulation of DSG2 by hypoxia was key to this process, as down-regulation of DSG2 in hypoxic regions of primary tumors led to elevated epithelial-mesenchymal transition (EMT) gene expression, allowing cells to detach from the primary tumor and undergo intravasation. Subsequent derepression of DSG2 after intravasation and release of hypoxic stress was associated with an increased ability to colonize distant organs. This dynamic regulation of DSG2 was mediated by Hypoxia-Induced Factor1α (HIF1α). In contrast to its more widely observed function to promote expression of hypoxia-inducible genes, HIF1α repressed DSG2 by recruitment of the polycomb repressive complex 2 components, EZH2 and SUZ12, to the DSG2 promoter in hypoxic cells. Consistent with our experimental data, DSG2 expression level correlated with poor prognosis and recurrence risk in breast cancer patients. Together, these results demonstrated the importance of DSG2 expression in metastasis and revealed a mechanism by which hypoxia drives metastasis.
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