ArticleCancer research2016
HEATR1 Negatively Regulates Akt to Help Sensitize Pancreatic Cancer Cells to Chemotherapy.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Computational Identification of Novel Stage-Specific Biomarkers in Colorectal Cancer Progression.PloS one · 2016Pooled it
- AMPK-activated BAP1 regulates pVHL stability and tumor-suppressive functions.Cell death and differentiation · 2026Article
- Phosphorylation of USP33 by CDK1 stabilizes the mTORC2 component SIN1.Cell death & disease · 2025Article
- Article
- Article
- Silencing HEATR1 Rescues Cisplatin Resistance of Non-small Cell Lung Cancer by Inducing FerroptosisCurrent cancer drug targets · 2025Article
- Identification of biomarkers based on ubiquitin-correlated genes for predicting immune profile and drug sensitivity in lung adenocarcinoma.Frontiers in pharmacology · 2025Article
- Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth.EMBO reports · 2024Article
- Article
- RRP9 promotes gemcitabine resistance in pancreatic cancer via activating AKT signaling pathway.Cell communication and signaling : CCS · 2022Article
- Role of the PP2A Pathway in Cholangiocarcinoma: State of the Art and Future Perspectives.Cancers · 2022Article
- A new era: tumor microenvironment in chemoresistance of pancreatic cancer.Journal of cancer science and clinical therapeutics · 2022Article
- Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression.Signal transduction and targeted therapy · 2021Review
- PROM2 promotes gemcitabine chemoresistance via activating the Akt signaling pathway in pancreatic cancer.Experimental & molecular medicine · 2020Article
- HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer.Journal of oncology · 2020Article
- HEATR1 deficiency promotes pancreatic cancer proliferation and gemcitabine resistance by up-regulating Nrf2 signaling.Redox biology · 2020Article
- Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells - Role of Snail, Slug and Twist and Small Molecule Inhibitors.OncoTargets and therapy · 2020Article
- Article
- Development of somatic mutation signatures for risk stratification and prognosis in lung and colorectal adenocarcinomas.BMC medical genomics · 2019Article
- Gestational Tissue-Derived Human Mesenchymal Stem Cells Use Distinct Combinations of Bioactive Molecules to Suppress the Proliferation of Human Hepatoblastoma and Colorectal Cancer Cells.Stem cells international · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Elucidating mechanisms of chemoresistance is critical to improve cancer therapy, especially for the treatment of pancreatic ductal adenocarcinoma (PDAC). Genome-wide association studies have suggested the less studied gene HEAT repeat-containing protein 1 (HEATR1) as a possible determinant of cellular sensitivity to different chemotherapeutic drugs. In this study, we assessed this hypothesized link in PDAC, where HEATR1 expression is downregulated significantly. HEATR1 silencing in PDAC cells increased resistance to gemcitabine and other chemotherapeutics, where this effect was associated with increased AKT kinase phosphorylation at the Thr308 regulatory site. Mechanistically, HEATR1 enhanced cell responsiveness to gemcitabine by acting as a scaffold to facilitate interactions between AKT and the protein phosphatase PP2A, thereby promoting Thr308 dephosphorylation. Consistent with these findings, treatment with the AKT inhibitor triciribine sensitized HEATR1-depleted PDAC cells to gemcitabine, suggesting that this therapeutic combination may overcome gemcitabine resistance in patients with low HEATR1 expression. Clinically, we found that HEATR1 downregulation in PDAC patients was associated with increased AKT phosphorylation, poor response to tumor resection plus gemcitabine standard-of-care treatment, and shorter overall survival. Collectively, our findings establish HEATR1 as a novel regulator of AKT and a candidate predictive and prognostic indicator of drug responsiveness and outcome in PDAC patients.
Indexed as
Identifiers
What OpenQuestion holds
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.