ArticleStem cell research & therapy2022
Radiochemotherapy-induced DNA repair promotes the biogenesis of gastric cancer stem cells.
Article in Stem cell research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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14 citing papers in PubMed, 16 citations in OpenAlex.
- IRF4 Enhances Radiosensitivity of Cervical Cancer by Inhibiting the PI3K/Akt/mTOR Pathway to Regulate Autophagy.Cancer science · 2026Article
- Current Perspectives on Radiosensitizers in Cancer Radiotherapy.International journal of nanomedicine · 2026Review
- Cisplatin-mediated activation of NF-κB promotes lung cancer stem cell formation via DNA repair pathways.Journal of translational medicine · 2025Article
- JMJD3 upregulates ALOX5 to drive malignancy and concomitant ferroptosis sensitivity in gastric cancer.Cell death & disease · 2025Article
- KLF4 in cancer chemoresistance: molecular mechanisms and therapeutic implications.Discover oncology · 2025Review
- Review
- HJURP modulates cell proliferation and chemoresistance via the MYC/TOP2A transcriptional axis in gastric cancer.Frontiers in molecular biosciences · 2025Article
- Gastric Adenocarcinoma with Enteroblastic Differentiation.Pathobiology : journal of immunopathology, molecular and cellular biology · 2025Review
- Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.Frontiers in cell and developmental biology · 2025Review
- Dynamic single-cell sequencing unveils the tumor microenvironment evolution of gastric cancer abdominal wall metastases during radiotherapy.Cancer science · 2024Article
- Antiviral Shrimp lncRNA06 Possesses Anti-Tumor Activity by Inducing Apoptosis of Human Gastric Cancer Stem Cells in a Cross-Species Manner.Marine drugs · 2024Article
- Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies.Journal of experimental & clinical cancer research : CR · 2024Review
- High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells.Cancers · 2023Article
- Krüppel-Like Factor 2 Is a Gastric Cancer Suppressor and Prognostic Biomarker.Evidence-based complementary and alternative medicine : eCAM · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClinically, metastasis and recurrence occurred after routine radiochemotherapy in dozens of cases of gastric cancer, mainly attributed to the role of cancer stem cells (CSCs). Actually, radiochemotherapy could induce DNA damages, leading to activation of DNA repair which might be associated with acquisition of stem cell phenotype. Hitherto, the contribution made by active DNA repair to stemness induction has not been extensively explored.
methodsCisplatin/doxorubicin treatment and X-ray exposure were conducted in gastric cancer cell lines and gastric cancer cells derived from solid tumors to model clinical therapy. Quantitative real-time PCR, Western blot, and tumorsphere/tumor formation assay were further used to characterize CSCs and assess activation of DNA repair. RNA-seq was performed to identify which DNA repair genes were crucial for CSC traits induction, followed by the investigation of underlying mechanism and functional significance via in vitro and in vivo experiments.
resultsHere, we report a mechanism through which gastric cancer cells in response to radiochemotherapy were reprogrammed into gastric cancer stem cell-like cells. In this mechanism, radiochemotherapy triggers DNA damage response accompanied by elevated levels of EID3, a typical DNA repair gene, which interacts with NAMPT to promote stemness via upregulating Wnt signaling pathway, manifested by enhanced tumorsphere/tumor formation in gastric cancer. In addition to involvement of EID3 in stemness acquisition, it also shows impacts on proliferation, cell cycle, apoptosis and therapy resistance to maintain the characteristics of CSC populations.
conclusionOur study indicates that gastric cancer cells can be endowed with stemness traits via EID3-NAMPT-Wnt/β-catenin axis in response to radiochemotherapy. Blocking this axis (i.e., targeting EID3) along with radiochemotherapy might represent a potential strategy to sensitize CSCs to radiochemotherapy and further reinforce the anti-tumor effects of conventional treatments.
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