ArticleCancer science2015
Sirtuin 6 promotes transforming growth factor-β1/H2O2/HOCl-mediated enhancement of hepatocellular carcinoma cell tumorigenicity by suppressing cellular senescence.
Article in Cancer science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- Advances in endogenous hypochlorous acid-mediated regulation of tumor cell fates.Frontiers in cell and developmental biology · 2026Review
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- The spatiotemporal heterogeneity of reactive oxygen species in the malignant transformation of viral hepatitis to hepatocellular carcinoma: a new insight.Cellular & molecular biology letters · 2025Review
- Roles of anoikis in hepatocellular carcinoma: mechanisms and therapeutic potential.Medical oncology (Northwood, London, England) · 2025Review
- Targeting sirtuins for cancer therapy: epigenetics modifications and beyond.Theranostics · 2024Review
- LncRNA NEAT1 suppresses cellular senescence in hepatocellular carcinoma via KIF11-dependent repression of CDKN2A.Clinical and translational medicine · 2023Article
- Review
- CDK4/6 inhibitors improve the anti-tumor efficacy of lenvatinib in hepatocarcinoma cells.Frontiers in oncology · 2022Article
- Anoikis resistance in diffuse glioma: The potential therapeutic targets in the future.Frontiers in oncology · 2022Review
- Emerging Therapeutic Potential of SIRT6 Modulators.Journal of medicinal chemistry · 2021Review
- Emerging roles of SIRT6 in human diseases and its modulators.Medicinal research reviews · 2021Review
- Sirtuins as Important Factors in Pathological States and the Role of Their Molecular Activity Modulators.International journal of molecular sciences · 2021Review
- Sirtuins at the Service of Healthy Longevity.Frontiers in physiology · 2021Review
- FOXO3a‑SIRT6 axis suppresses aerobic glycolysis in melanoma.International journal of oncology · 2020Article
- The sirtuin 6: An overture in skin cancer.Experimental dermatology · 2020Review
- Sirtuin 6 deficiency transcriptionally up-regulates TGF-β signaling and induces fibrosis in mice.The Journal of biological chemistry · 2020Article
- Hepatocellular Senescence: Immunosurveillance and Future Senescence-Induced Therapy in Hepatocellular Carcinoma.Frontiers in oncology · 2020Review
- The sirtuin family in cancer.Cell cycle (Georgetown, Tex.) · 2019Article
- SIRT6 regulates the proliferation and apoptosis of hepatocellular carcinoma via the ERK1/2 signaling pathway.Molecular medicine reports · 2019Article
- Inhibition of Sirt6 suppresses tumor growth by inducing G1/S phase arrest in renal cancer cells.International journal of clinical and experimental pathology · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sirtuin 6 (SIRT6) can function as a tumor suppressor by suppressing aerobic glycolysis and apoptosis resistance. However, the negative effect of SIRT6 on cellular senescence implies that it may also have the potential to promote tumor development. Here we report that the upregulation of SIRT6 expression was required for transforming growth factor (TGF)-β1 and H2O2/HOCl reactive oxygen species (ROS) to promote the tumorigenicity of hepatocellular carcinoma (HCC) cells. Transforming growth factor-β1/H2O2/HOCl could upregulate SIRT6 expression in HCC cells by inducing the sustained activation of ERK and Smad pathways. Sirtuin 6 in turn abrogated the inducing effect of TGF-β1/H2O2/HOCl on cellular senescence of HCC cells, and was required for the ERK pathway to efficiently suppress the expression of p16 and p21. Sirtuin 6 altered the effect of Smad and p38 MAPK pathways on cellular senescence, and contributed to the inhibitory effect of the ERK pathway on cellular senescence. However, SIRT6 was inefficient in antagonizing the promoting effect of TGF-β1/H2O2 HOCl on aerobic glycolysis and anoikis resistance. Intriguingly, if SIRT6 expression was inhibited, the promoting effect of TGF-β1/H2O2/HOCl on aerobic glycolysis and anoikis resistance was not sufficient to enhance the tumorigenicity of HCC cells. Suppressing the upregulation of SIRT6 enabled TGF-β1/H2O2/HOCl to induce cellular senescence, thereby abrogating the enhancement of HCC cell tumorigenicity by TGF-β1/H2O2/HOCl. These results suggest that SIRT6 is required for TGF-β1/H2O2/HOCl to enhance the tumorigenicity of HCC cells, and that targeting the ERK pathway to suppress the upregulation of SIRT6 might be a potential approach in comprehensive strategies for the therapy of HCC.
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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.