ArticleCancer medicine2022
SPP1 promotes radiation resistance through JAK2/STAT3 pathway in esophageal carcinoma.
Article in Cancer medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Unveiling the role of ANGPT2 in esophageal cancer: A prognostic factor and potential oncogene.Oncology reports · 2026Article
- The cost of persistent alarm: temporal transcriptional reprogramming of macrophages from acute activation to chronic immune suppression by day 11.Frontiers in immunology · 2026Article
- SKA3 promotes cell growth and metastasis and is associated with poor prognosis in patients with esophageal cancer.American journal of translational research · 2026Article
- The role of SPP1 in evaluating the prognosis, immune infiltration, and drug sensitivity of hepatocellular carcinoma.PloS one · 2026Article
- SPP1 regulates tumor progression through modulation of signaling pathways and the tumor microenvironment.Discover oncology · 2025Review
- The crucial role of SPP1 in osteoporosis, osteoarthritis, and cancer.Pharmaceutical science advances · 2025Review
- SPP1Scientific reports · 2025Article
- Interactions between cancer-associated fibroblasts and the extracellular matrix in oesophageal cancer.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Integrated multi-omics analysis and machine learning refine molecular subtypes and clinical outcome for hepatocellular carcinoma.Hereditas · 2025Article
- Enhancement of radio-sensitivity by inhibition of Janus kinase signaling with oclacitinib in canine tumor cell lines.Molecular therapy. Oncology · 2025Article
- Prognostic values of intracellular cell-related genes in esophageal cancer and their regulatory mechanisms.BMC cancer · 2025Article
- Bioinformatic characterization of STING expression in hematological malignancies reveals association with prognosis and anti-tumor immunity.Frontiers in immunology · 2025Article
- ML385 promotes ferroptosis and radiotherapy sensitivity by inhibiting the NRF2-SLC7A11 pathway in esophageal squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2024Article
- SPP1 promotes tumor progression in esophageal carcinoma by activating focal adhesion pathway.Journal of gastrointestinal oncology · 2024Article
- Targeting the cGAS-STING Pathway Inhibits Peripheral T-cell Lymphoma Progression and Enhances the Chemotherapeutic Efficacy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The oncogenic mechanisms of the Janus kinase-signal transducer and activator of transcription pathway in digestive tract tumors.Cell communication and signaling : CCS · 2024Review
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- Role of SPP1 in the diagnosis of gastrointestinal cancer.Oncology letters · 2023Article
- Inhibition of protein kinase C isozymes causes immune profile alteration and possibly decreased tumorigenesis in bladder cancer.American journal of cancer research · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTherapeutic resistance to radiotherapy is one of the major obstacles in clinical practice that significantly affect the therapeutic efficiency and prognosis of human esophageal carcinoma (ESCA). Thus, it is critical to understand the molecular mechanisms of radiation resistance in ESCA. Secreted phosphoprotein 1 (SPP1) plays an essential role in various human cancers, but its role in radiation resistance remains unclear.
methodCell culture and transfection; Cell Counting Kit-8 (CCK-8) assays; EdU incorporation assays; Patient sample collection and medical records review; Transwell assays; Colony formation assays; Wound healing assays; Western blot; Immunofluorescence; Immunohistochemistry; Irradiation; Flow cytometry; Animal studies; Human Apoptosis Array Kit; Bioinformatics.
resultIn the current study, we reported the novel phenomenon that radiation-treated human ESCA cells upregulated SPP1 expression, which in turn contributed to the ESCA resistance to radiotherapy. We also reported the tumor-promoting effect of SPP1 in ESCA systematically and comprehensively. Furthermore, subsequent studies by knocking down or overexpressing SPP1 in human ESCA cells showed that SPP1 could facilitate the repair of DNA damage and the survival of tumor cells post-radiation in ESCA, which might contribute to the development of radiation resistance during the radiotherapy process. More detailed investigations on the downstream molecular pathway suggested that radiation could increase the phosphorylation level of JAK2 and STAT3 by increasing SPP1 expression. Further in vivo validation using a mouse ESCA xenograft model showed that SPP1 overexpression significantly increased tumor volume while either SPP1 knockdown or pharmacological inhibition of the JAK2-STAT3 pathway reduced tumor volume in a synergistic manner with radiotherapy.
conclusionCollectively, these findings suggested that the SPP1/JAK2/STAT3 axis is a critical player in ESCA progression and radiation resistance, which is a potential therapeutic target for combined therapy with the standard radiotherapy regimen to improve curative effect and increase patients' survival with ESCA.
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