ArticleExperimental & molecular medicine2018
TGF-β downregulation-induced cancer cell death is finely regulated by the SAPK signaling cascade.
Article in Experimental & molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
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- Combined downregulation of TGF-β1 and GRP78 is responsible for overcoming acquired sorafenib resistance, which is initiated by rewiring the cell surface CD44-GRP78-IGF-1R signaling circuit.Cancer gene therapy · 2025Article
- Interleukin-1 receptor antagonist overexpression in mesenchymal stem cells improves hemorrhagic cystitis outcomes via HtrA serine peptidase 3.Stem cell research & therapy · 2025Article
- Enhancing Gene Delivery to Breast Cancer with Highly Efficient siRNA Loading and pH-Responsive Small Extracellular Vesicles.ACS biomaterials science & engineering · 2025Article
- Therapeutic effects ofFrontiers in pharmacology · 2025Article
- Anti-fibrogenic effect of umbilical cord-derived mesenchymal stem cell-conditioned media in human esophageal fibroblasts.Scientific reports · 2024Article
- Implications of ZNF334 gene in lymph node metastasis of lung SCC: potential bypassing of cellular senescence.Journal of translational medicine · 2024Article
- The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.Current cancer drug targets · 2024Review
- Shaping the "hot" immunogenic tumor microenvironment by nanoparticles co-delivering oncolytic peptide and TGF-β1 siRNA for boosting checkpoint blockade therapy.Bioengineering & translational medicine · 2023Article
- Tumor-derived interleukin-1 receptor antagonist exhibits immunosuppressive functions and promotes pancreatic cancer.Cell & bioscience · 2023Article
- Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer.International journal of molecular sciences · 2023Review
- Enhanced tumor targeting and timely viral release of mesenchymal stem cells/oncolytic virus complex due to GRP78 and inducible E1B55K expressions greatly increase the antitumor effect of systemic treatment.Molecular therapy oncolytics · 2022Article
- Dexmedetomidine attenuates hippocampal neuroinflammation in postoperative neurocognitive disorders by inhibiting microRNA-329-3p and activating the CREB1/IL1RA axis.Psychopharmacology · 2022Article
- Targeting transforming growth factor-β signalling for cancer prevention and intervention: Recent advances in developing small molecules of natural origin.Clinical and translational medicine · 2022Review
- 3-Bromopyruvate inhibits pancreatic tumor growth by stalling glycolysis, and dismantling mitochondria in a syngeneic mouse model.American journal of cancer research · 2022Article
- The anti-tumour effect of induced pluripotent stem cells against submandibular gland carcinoma in rats is achieved via modulation of the apoptotic response and the expression of Sirt-1, TGF-β, and MALAT-1 in cancer cells.Molecular and cellular biochemistry · 2022Article
- TGFβ Signaling in the Pancreatic Tumor Microenvironment.Cancers · 2021Review
- Targeting circular RNAs as a therapeutic approach: current strategies and challenges.Signal transduction and targeted therapy · 2021Review
- New Anti-Leukemic Effect of Carvacrol and Thymol Combination through Synergistic Induction of Different Cell Death Pathways.Molecules (Basel, Switzerland) · 2021Article
- Cancer-Associated Fibroblasts Facilitate Squamous Cell Carcinoma Lung Metastasis in Mice by Providing TGFβ-Mediated Cancer Stem Cell Niche.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transforming growth factor (TGF)-β signaling is increasingly recognized as a key driver in cancer. In progressive cancer tissues, TGF-β promotes tumor formation, and its increased expression often correlates with cancer malignancy. In this study, we utilized adenoviruses expressing short hairpin RNAs against TGF-β1 and TGF-β2 to investigate the role of TGF-β downregulation in cancer cell death. We found that the downregulation of TGF-β increased the phosphorylation of several SAPKs, such as p38 and JNK. Moreover, reactive oxygen species (ROS) production was also increased by TGF-β downregulation, which triggered Akt inactivation and NOX4 increase-derived ROS in a cancer cell-type-specific manner. We also revealed the possibility of substantial gene fluctuation in response to TGF-β downregulation related to SAPKs. The expression levels of Trx and GSTM1, which encode inhibitory proteins that bind to ASK1, were reduced, likely a result of the altered translocation of Smad complex proteins rather than from ROS production. Instead, both ROS and ROS-mediated ER stress were responsible for the decrease in interactions between ASK1 and Trx or GSTM1. Through these pathways, ASK1 was activated and induced cytotoxic tumor cell death via p38/JNK activation and (or) induction of ER stress.
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