ArticleOncotarget2016
Oncogenic K-ras confers SAHA resistance by up-regulating HDAC6 and c-myc expression.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
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- The Potential of Senescence as a Target for Developing Anticancer Therapy.International journal of molecular sciences · 2023Review
- Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers.JCI insight · 2022Article
- Dual Inhibition of Myc Transcription and PI3K Activity Effectively Targets Colorectal Cancer Stem Cells.Cancers · 2022Article
- Suberoylanilide Hydroxamic Acid (SAHA) Treatment Reveals Crosstalk Among Proteome, Phosphoproteome, and Acetylome in Nasopharyngeal Carcinoma Cells.Frontiers in genetics · 2022Article
- PI3K-driven HER2 expression is a potential therapeutic target in colorectal cancer stem cells.Gut · 2022Article
- Upregulation of ERK-EGR1-heparanase axis by HDAC inhibitors provides targets for rational therapeutic intervention in synovial sarcoma.Journal of experimental & clinical cancer research : CR · 2021Article
- Stress granules in colorectal cancer: Current knowledge and potential therapeutic applications.World journal of gastroenterology · 2020Review
- Pin1 coordinates HDAC6 upregulation with cell migration in lung cancer cells.International journal of medical sciences · 2020Article
- Rational cotargeting of HDAC6 and BET proteins yields synergistic antimyeloma activity.Blood advances · 2019Article
- Silencing of HDAC6 as a therapeutic target in chronic lymphocytic leukemia.Blood advances · 2018Article
- Class I HDAC Inhibitors Display Different Antitumor Mechanism in Leukemia and Prostatic Cancer Cells Depending on Their p53 Status.Journal of medicinal chemistry · 2018Article
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- NRAS mutations in cutaneous T cell lymphoma (CTCL) sensitize tumors towards treatment with the multikinase inhibitor Sorafenib.Oncotarget · 2017Article
- The role of prostate tumor overexpressed 1 in cancer progression.Oncotarget · 2017Review
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- The identification and validation of Trichosstatin A as a potential inhibitor of colon tumorigenesis and colon cancer stem-like cells.American journal of cancer research · 2017Article
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- Gigantol Targets MYC for Ubiquitin-proteasomal Degradation and Suppresses Lung Cancer Cell Growth.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase inhibitors (HDIs) represent a new class of anticancer drugs. Suberoylanilide hydroxamic acid (SAHA), the first HDI approved for the treatment of cutaneous T cell lymphoma (CTCL), is currently being tested in clinical trials for other cancers. However, SAHA has been ineffective against solid tumors in many clinical trials. A better understanding of molecular mechanisms of SAHA resistance may provide the basis for improved patient selection and the enhancement of clinical efficacy. Here we demonstrate that oncogenic K-ras contributes to SAHA resistance by upregulating HDAC6 and c-myc expression. We find that the high levels of HDAC6 expression are associated with activated K-ras mutant in colon cancer patients. And expressions of HDAC6 and c-myc are increased in fibroblasts transformed with activated K-ras. Surprisingly, we find that activated K-ras transformed cells are more resistant to SAHA inhibition on cell growth and anchorage-independent colony formation. We show that a K-ras inhibitor sensitizes K-ras mutated lung cancer cells to SAHA induced growth inhibition. We also find that mutant K-ras induces HDAC6 expression by a MAP kinase dependent pathway. Our study suggests that combined treatment with SAHA and K-ras inhibitors may represent an effective strategy to overcome SAHA resistance.
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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.