ArticleEBioMedicine2019
TGFβ induces stemness through non-canonical AKT-FOXO3a axis in oral squamous cell carcinoma.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Cancer-associated fibroblasts as a target in head and neck squamous cell carcinoma: bridging mechanisms to therapy with drugs, adjuvants, and nanotechnology.Discover oncology · 2026Review
- Stiffness-related stress granules promote the metastasis of early-stage oral squamous cell carcinoma via anoikis resistance.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- From Environmental Risk to Cancer Stemness: Epigenetic Regulation in Oral Squamous Cell Carcinoma.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Molecular signatures of disulfidptosis: interplay with programmed cell death pathways and therapeutic implications in oncology.Cellular & molecular biology letters · 2025Review
- An anti-FAP-scFv-functionalized exosome-carrying hydrogel deliversTheranostics · 2025Article
- Role of exosomes in transforming growth factor-β-mediated cancer cell plasticity and drug resistance.Exploration of targeted anti-tumor therapy · 2025Review
- Disulfide stress and its role in cardiovascular diseases.Redox biology · 2024Review
- Stabilization of TGF-β Receptor 1 by a Receptor-Associated Adaptor Dictates Feedback Activation of the TGF-β Signaling Pathway to Maintain Liver Cancer Stemness and Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.Redox biology · 2024Review
- ZNF677 inhibits oral squamous cell carcinoma growth and tumor stemness by regulating FOXO3a.Human cell · 2023Article
- Tumour-associated macrophages: versatile players in the tumour microenvironment.Frontiers in cell and developmental biology · 2023Review
- Receptor, Signal, Nucleus, Action: Signals That Pass through Akt on the Road to Head and Neck Cancer Cell Migration.Cancers · 2022Review
- Autophagy regulates the cancer stem cell phenotype of head and neck squamous cell carcinoma through the noncanonical FOXO3/SOX2 axis.Oncogene · 2022Article
- FGFR2 maintains cancer cell differentiation via AKT signaling in esophageal squamous cell carcinoma.Cancer biology & therapy · 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
- TGF-β Signaling and Resistance to Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- Precision Medicine Gains Momentum: Novel 3D Models and Stem Cell-Based Approaches in Head and Neck Cancer.Frontiers in cell and developmental biology · 2021Review
- Radiotherapy targeting cancer stem cells "awakens" them to induce tumour relapse and metastasis in oral cancer.International journal of oral science · 2020Review
- Targeting the non-canonical AKT-FOXO3a axis: A potential therapeutic strategy for oral squamous cell carcinoma.EBioMedicine · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFOXO3a has been widely regarded as a tumor suppressor. It also plays a paradoxical role in regulating the cancer stem cells (CSCs), responsible for tumor-initiation, chemo-resistance, and recurrence in various solid tumors, including oral squamous cell carcinoma (OSCC). This study aims to uncover the role of FOXO3a and its importance for a non-canonical pathway of TGFβ in regulating the OSCC stemness.
methodsWe identified FOXO3a expression in OSCC tissues and cell lines using immunohistochemistry and western blot. The correlation between FOXO3a and stemness was evaluated. Stable cell lines with differential expression of FOXO3a were constructed using lentiviruses. The effects of FOXO3a on stem-cell like properties in OSCC was further evaluated in vitro and in vivo. We also explored the effect of TGFβ on FOXO3a with respect to its expression and function.
findingsOur findings suggest that FOXO3a was widely expressed and negatively correlated with the stemness in OSCC. This regulation can be abolished by TGFβ through phosphorylation, nuclear exclusion, and degradation in the non-Smad pathway. We also observed that non-Smad AKT-FOXO3a axis is essential to regulate stemness of CSCs by TGFβ.
interpretationTGFβ induces stemness through non-canonical AKT-FOXO3a axis in OSCC. Our study provides a foundation to understand the mechanism of CSCs and a possible therapeutic target to eliminate CSCs.
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