ArticleInternational journal of molecular sciences2020
Deficiency in Dipeptidyl Peptidase-4 Promotes Chemoresistance through the CXCL12/CXCR4/mTOR/TGFβ Signaling Pathway in Breast Cancer Cells.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Changes in the metabolism of axillary lymph node cells as a predictor of regional metastasis in breast cancer.World journal of experimental medicine · 2026Article
- Assessing the therapeutic effects of DPP4 Inhibitors on TGF-β2-induced Lens Opacity.Experimental eye research · 2026Article
- DPP-4 Inhibitors in Female Cancers: Opportunities for Drug Repurposing.Current issues in molecular biology · 2026Review
- Smart Physicochemical-triggered Chitosan-based Nanogels for siRNA Delivery and Gene Therapy: A Focus on Emerging Strategies and Paradigms for Cancer Therapy.Current medicinal chemistry · 2025Review
- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- Dual blockade of DPP-4 and CXCL12/CXCR4 axes synergistically protects podocytes in lupus nephritis.Frontiers in pharmacology · 2025Article
- A case of immunoglobulin G4-related kidney disease manifesting after dipeptidyl peptidase-4 inhibitor treatment.CEN case reports · 2024Article
- Cancer biology in diabetes update: Focusing on antidiabetic drugs.Journal of diabetes investigation · 2024Review
- Article
- Crosstalk between CaInternational journal of molecular sciences · 2022Review
- Does DPP-IV Inhibition Offer New Avenues for Therapeutic Intervention in Malignant Disease?Cancers · 2022Review
- Past, Present and Future: The Relationship Between Circular RNA and Immunity.Frontiers in immunology · 2022Review
- DPP4 gene silencing inhibits proliferation and epithelial-mesenchymal transition of papillary thyroid carcinoma cells through suppression of the MAPK pathway.Journal of endocrinological investigation · 2021Article
- Review
- The Breast Cancer Stem Cells Traits and Drug Resistance.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dipeptidyl peptidase (DPP)-4, a molecular target of DPP-4 inhibitors, which are type 2 diabetes drugs, is expressed in a variety of cell types, tissues and organs. DPP-4 has been shown to be involved in cancer biology, and we have recently shown that a DPP-4 inhibitor promoted the epithelial mesenchymal transition (EMT) in breast cancer cells. The EMT is known to associate with chemotherapy resistance via the induction of ATP-binding cassette (ABC) transporters in cancer cells. Here, we demonstrated that deficiency in DPP-4 promoted chemotherapy resistance via the CXCL12/CXCR4/mTOR axis, activating the TGFβ signaling pathway via the expression of ABC transporters. DPP-4 inhibition enhanced ABC transporters in vivo and in vitro. Doxorubicin (DOX) further induced ABC transporters in DPP-4-deficient 4T1 cells, and the induction of ABC transporters was suppressed by either the CXCR4 inhibitor AMD3100, the mTOR inhibitor rapamycin or a neutralizing TGFβ (1, 2 and 3) antibody(N-TGFβ). Knockdown of snail, an EMT-inducible transcription factor, suppressed ABC transporter levels in DOX-treated DPP-4-deficient 4T1 cells. In an allograft mouse model, however, the effects of DOX in either primary tumor or metastasis were not statistically different between control and DPP-4-kd 4T1. Taken together, our findings suggest that DPP-4 inhibitors potentiate chemotherapy resistance via the induction of ABC transporters by the CXCL12/CXCR4/mTOR/TGFβ signaling pathway in breast cancer cells.
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