ArticleCell death & disease2016
AKT activation controls cell survival in response to HDAC6 inhibition.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Pharmacological manipulation of liver fibrosis progression using novel HDAC6 inhibitors.The FEBS journal · 2025Article
- Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer.Pharmaceutics · 2023Review
- Inhibition of histone deacetylase 6 destabilizes ERK phosphorylation and suppresses cancer proliferation via modulation of the tubulin acetylation-GRP78 interaction.Journal of biomedical science · 2023Article
- Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance.International journal of molecular sciences · 2022Review
- Evaluation of the Therapeutic Potential of Histone Deacetylase 6 Inhibitors for Primary and Metastatic Uveal Melanoma.International journal of molecular sciences · 2022Review
- Rictor/mTORC2 involves mitochondrial function in ES cells derived cardiomyocytes via mitochondrial Connexin 43.Acta pharmacologica Sinica · 2021Article
- Dysregulation of LINC00470 and METTL3 promotes chemoresistance and suppresses autophagy of chronic myelocytic leukaemia cells.Journal of cellular and molecular medicine · 2021Article
- HDAC6 is associated with the formation of aortic dissection in human.Molecular medicine (Cambridge, Mass.) · 2019Article
- IDO1 and Kynurenine Pathway Metabolites Activate PI3K-Akt Signaling in the Neoplastic Colon Epithelium to Promote Cancer Cell Proliferation and Inhibit Apoptosis.Cancer research · 2019Article
- Valproate reduces neuroinflammation and neuronal death in a rat chronic constriction injury model.Scientific reports · 2018Article
- The HDAC6 inhibitor C1A modulates autophagy substrates in diverse cancer cells and induces cell death.British journal of cancer · 2018Article
- Long noncoding RNA HULC accelerates liver cancer by inhibiting PTEN via autophagy cooperation to miR15a.Molecular cancer · 2018Article
- Lysine Deacetylation by HDAC6 Regulates the Kinase Activity of AKT in Human Neural Progenitor Cells.ACS chemical biology · 2017Article
- Kallistatin exerts anti-lymphangiogenic effects by inhibiting lymphatic endothelial cell proliferation, migration and tube formation.International journal of oncology · 2017Article
- Inhibition of HDAC6 protects against rhabdomyolysis-induced acute kidney injury.American journal of physiology. Renal physiology · 2017Article
- Valproate Attenuates Endoplasmic Reticulum Stress-Induced Apoptosis in SH-SY5Y Cells via the AKT/GSK3β Signaling Pathway.International journal of molecular sciences · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
HDAC6 is emerging as an important therapeutic target for cancer. We investigated mechanisms responsible for survival of tumor cells treated with a HDAC6 inhibitor. Expression of the 20 000 genes examined did not change following HDAC6 treatment in vivo. We found that HDAC6 inhibition led to an increase of AKT activation (P-AKT) in vitro, and genetic knockdown of HDAC6 phenocopied drug-induced AKT activation. The activation of AKT was not observed in PTEN null cells; otherwise, PTEN/PIK3CA expression per se did not predict HDAC6 inhibitor sensitivity. Interestingly, HDAC6 inhibitor treatment led to inactivating phosphorylation of PTEN (P-PTEN Ser380), which likely led to the increased P-AKT in cells that express PTEN. Synergy was observed with phosphatidylinositol 3'-kinases (PI3K) inhibitor treatment in vitro, accompanied by increased caspase 3/7 activity. Furthermore, combination of HDAC6 inhibitor with a PI3K inhibitor caused substantial tumor growth inhibition in vivo compared with either treatment alone, also detectable by Ki-67 immunostaining and (18)F-FLT positron emission tomography (PET). In aggregate AKT activation appears to be a key survival mechanism for HDAC6 inhibitor treatment. Our findings indicate that dual inhibition of HDAC6 and P-AKT may be necessary to substantially inhibit growth of solid tumors.
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Registered trials
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.