ArticleOncotarget2015
Intrinsic TGF-β2-triggered SDF-1-CXCR4 signaling axis is crucial for drug resistance and a slow-cycling state in bone marrow-disseminated tumor cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- G protein-coupled receptors as novel therapeutic targets in non-small-cell lung cancer.Medical review (2021) · 2025Review
- CXC chemokine receptor 4 (CXCR4) blockade in cancer treatment.Journal of cancer research and clinical oncology · 2023Review
- CXCL12 is expressed by skeletal muscle cells in tongue oral squamous cell carcinoma.Cancer medicine · 2023Article
- Single-Cell Transcriptome Analysis Reveals Changes of Tumor Immune Microenvironment in Oral Squamous Cell Carcinoma After Chemotherapy.Frontiers in cell and developmental biology · 2022Article
- Slow-cycling (dormant) cancer cells in therapy resistance, cancer relapse and metastasis.Seminars in cancer biology · 2022Review
- Synergistic enhancement of efficacy of platinum drugs with verteporfin in ovarian cancer cells.BMC cancer · 2020Article
- The effects of proliferation status and cell cycle phase on the responses of single cells to chemotherapy.Molecular biology of the cell · 2020Article
- Circulating osteopontin per tumor volume as a prognostic biomarker for resectable intrahepatic cholangiocarcinoma.Hepatobiliary surgery and nutrition · 2019Article
- Memantine, a Noncompetitive N-Methyl-D-Aspartate Receptor Antagonist, Attenuates Cerebral Amyloid Angiopathy by Increasing Insulin-Degrading Enzyme Expression.Molecular neurobiology · 2019Article
- CCR7 high expression leads to cetuximab resistance by cross-talking with EGFR pathway in PI3K/AKT signals in colorectal cancer.American journal of cancer research · 2019Article
- Bone metastases from head and neck malignancies: Prognostic factors and skeletal-related events.PloS one · 2019Observational
- Potential Role of CXCR4 Targeting in the Context of Radiotherapy and Immunotherapy of Cancer.Frontiers in immunology · 2018Review
- TGF-β-Dependent Growth Arrest and Cell Migration in Benign and Malignant Breast Epithelial Cells Are Antagonistically Controlled by Rac1 and Rac1b.International journal of molecular sciences · 2017Article
- Regorafenib inhibited gastric cancer cells growth and invasion via CXCR4 activated Wnt pathway.PloS one · 2017Article
- Lymph Nodes and Cancer Metastasis: New Perspectives on the Role of Intranodal Lymphatic Sinuses.International journal of molecular sciences · 2016Review
- Axl is required for TGF-β2-induced dormancy of prostate cancer cells in the bone marrow.Scientific reports · 2016Article
- Role of stromal cell-derived factor 1α pathway in bone metastatic prostate cancer.Journal of biomedical research · 2016Review
- The biology and clinical implications of prostate cancer dormancy and metastasis.Journal of molecular medicine (Berlin, Germany) · 2016Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Dormant or slow-cycling disseminated tumor cells (DTCs) in bone marrow (BM) are resistant to conventional therapy in various cancers including head and neck squamous cell carcinoma (HNSCC), although the molecular mechanisms remain largely unknown. This study aimed to identify the intrinsic molecular mechanisms underlying drug resistance in BM-DTCs. We used in vivo selection of the human HNSCC cell line HEp3, which mimics non-proliferative BM-DTCs in mice, to establish BM-DTC-derived (BM-HEp3) and lung metastases-derived (Lu-HEp3) sublines. Both sublines had higher migration activity and shortened survival in a murine xenograft model compared with parental (P-HEp3) cells. Slow-cycling BM-HEp3 cells had intrinsically enhanced cisplatin resistance compared with Lu-HEp3 cells, which also manifested this resistance but proliferated rapidly. The drug resistance and slow-cycling state of BM-HEp3 cells depended on enhanced positive feedback of the signaling axis of stromal cell-derived factor-1 (SDF-1)-C-X-C chemokine receptor-4 (CXCR4) via their overexpression. Interestingly, BM-DTCs highly expressed transforming growth factor-beta 2 (TGF-β2) to maintain SDF-1-CXCR4 overexpression. Inhibition of SDF-1-CXCR4 signaling by down-regulating TGF-β2 fully reversed the drug resistance of BM-HEp3 cells via reactivation of cell proliferation. These data suggest that the intrinsic TGF-β2-triggered SDF-1-CXCR4 signaling axis is crucial for drug resistance dependent on a slow-cycling state in BM-DTCs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.