ArticleMolecular & cellular proteomics : MCP2020
Upregulation of CD73 Confers Acquired Radioresistance and is Required for Maintaining Irradiation-selected Pancreatic Cancer Cells in a Mesenchymal State.
Article in Molecular & cellular proteomics : MCP, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Effect of Ipomoeassin F on the Synthesis of Membrane and Secretory Proteins in Triple-Negative Breast Cancer Cells.ACS omega · 2025Article
- Purinergic system in cancer stem cells.Purinergic signalling · 2025Review
- Efficacy and pharmacodynamic effect of anti-CD73 and anti-PD-L1 monoclonal antibodies in combination with cytotoxic therapy: observations from mouse tumor models.Cancer biology & therapy · 2024Article
- Proteomic Analysis Reveals Major Proteins and Pathways That Mediate the Effect of 17-β-Estradiol in Cell Division and Apoptosis in Breast Cancer MCF7 Cells.Journal of proteome research · 2024Article
- Regulation of CD73 on NAD metabolism: Unravelling the interplay between tumour immunity and tumour metabolism.Cell communication and signaling : CCS · 2024Review
- The Clinical Significance of CD73 in Cancer.International journal of molecular sciences · 2023Review
- A Novel Bispecific Antibody for EpCAM-Directed Inhibition of the CD73/Adenosine Immune Checkpoint in Ovarian Cancer.Cancers · 2023Article
- Acquired radioresistance in EMT6 mouse mammary carcinoma cell line is mediated by CTLA-4 and PD-1 through JAK/STAT/PI3K pathway.Scientific reports · 2023Article
- CD73, a Promising Therapeutic Target of Diclofenac, Promotes Metastasis of Pancreatic Cancer through a Nucleotidase Independent Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Tumor intrinsic and extrinsic functions of CD73 and the adenosine pathway in lung cancer.Frontiers in immunology · 2023Review
- ER translocon inhibitor ipomoeassin F inhibits triple-negative breast cancer growth via blocking ER molecular chaperones.International journal of biological sciences · 2023Article
- The clinical relevance of OSM in inflammatory diseases: a comprehensive review.Frontiers in immunology · 2023Review
- Evidence that cervical cancer cells cultured as tumorspheres maintain high CD73 expression and increase their protumor characteristics through TGF-β production.Cell biochemistry and function · 2022Article
- ALCAM: A Novel Surface Marker on EpCAMBiomedicines · 2022Article
- Targeting purinergic pathway to enhance radiotherapy-induced immunogenic cancer cell death.Journal of experimental & clinical cancer research : CR · 2022Review
- [An Overview and Interpretation of Important Clinical Studies on Non-small Cell Lung Cancer in 2021].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2022Review
- Noncoding RNAs Associated with Therapeutic Resistance in Pancreatic Cancer.Biomedicines · 2021Review
- Review
- Purinergic Signaling in Pancreas-From Physiology to Therapeutic Strategies in Pancreatic Cancer.International journal of molecular sciences · 2020Review
- Emerging roles for the IL-6 family of cytokines in pancreatic cancer.Clinical science (London, England : 1979) · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The molecular mechanisms underlying exceptional radioresistance in pancreatic cancer remain elusive. In the present study, we established a stable radioresistant pancreatic cancer cell line MIA PaCa-2-R by exposing the parental MIA PaCa-2 cells to fractionated ionizing radiation (IR). Systematic proteomics and bioinformatics analysis of protein expression in MIA PaCa-2 and MIA PaCa-2-R cells revealed that several growth factor-/cytokine-mediated pathways, including the OSM/STAT3, PI3K/AKT, and MAPK/ERK pathways, were activated in the radioresistant cells, leading to inhibition of apoptosis and increased epithelial-mesenchymal plasticity. In addition, the radioresistant cells exhibited enhanced capabilities of DNA repair and antioxidant defense compared with the parental cells. We focused functional analysis on one of the most up-regulated proteins in the radioresistant cells, ecto-5'-nucleotidase (CD73), which is a cell surface protein that is overexpressed in different types of cancer. Ectopic overexpression of CD73 in the parental cells resulted in radioresistance and conferred resistance to IR-induced apoptosis. Knockdown of CD73 re-sensitized the radioresistant cells to IR and IR-induced apoptosis. The effect of CD73 on radioresistance and apoptosis is independent of the enzymatic activity of CD73. Further studies demonstrate that CD73 up-regulation promotes Ser-136 phosphorylation of the proapoptotic protein BAD and is required for maintaining the radioresistant cells in a mesenchymal state. Our findings suggest that expression alterations in the IR-selected pancreatic cancer cells result in hyperactivation of the growth factor/cytokine signaling that promotes epithelial-mesenchymal plasticity and enhancement of DNA repair. Our results also suggest that CD73, potentially a novel downstream factor of the enhanced growth factor/cytokine signaling, confers acquired radioresistance by inactivating proapoptotic protein BAD via phosphorylation of BAD at Ser-136 and by maintaining the radioresistant pancreatic cancer cells in a mesenchymal state.
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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.