ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2017
Roles of autophagy and metabolism in pancreatic cancer cell adaptation to environmental challenges.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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
18 citing papers in PubMed, 29 citations in OpenAlex.
- Dual targeting of SLC6A14 and autophagy/macropinocytosis enhances therapeutic efficacy in pancreatic ductal adenocarcinoma.The Biochemical journal · 2026Article
- Hypoxia-Induced Metabolic and Functional Changes in Oral CSCs: Implications for Stemness and Viability Modulation Through BNIP3-Driven Mitophagy.Journal of cellular and molecular medicine · 2025Article
- Crosstalk between oxidative phosphorylation and immune escape in cancer: a new concept of therapeutic targets selection.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Gemcitabine promotes autophagy and lysosomal function through ERK- and TFEB-dependent mechanisms.Cell death discovery · 2023Article
- Cellular metabolism in pancreatic cancer as a tool for prognosis and treatment (Review).International journal of oncology · 2022Review
- Regulation and function of autophagy in pancreatic cancer.Autophagy · 2021Review
- Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression.iScience · 2021Article
- Targeting hypoxic tumor microenvironment in pancreatic cancer.Journal of hematology & oncology · 2021Review
- DDIT4 Novel Mutations in Pancreatic Cancer.Gastroenterology research and practice · 2021Article
- Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types.Frontiers in pharmacology · 2021Review
- The Role and Mechanism of Autophagy in Pancreatic Cancer: An Update Review.Cancer management and research · 2021Review
- Molecular and Metabolic Subtypes Correspondence for Pancreatic Ductal Adenocarcinoma Classification.Journal of clinical medicine · 2020Review
- Metabolism of pancreatic cancer: paving the way to better anticancer strategies.Molecular cancer · 2020Review
- Associations of novel variants inAmerican journal of cancer research · 2020Article
- High glucose microenvironment accelerates tumor growth via SREBP1-autophagy axis in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2019Article
- Review
- Natural Compound Methyl Protodioscin Suppresses Proliferation and Inhibits Glycolysis in Pancreatic Cancer.Evidence-based complementary and alternative medicine : eCAM · 2018Article
- Differences of basic and induced autophagic activity between K562 and K562/ADM cells.Intractable & rare diseases research · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) displays extensive and poorly vascularized desmoplastic stromal reaction, and therefore, pancreatic cancer (PaCa) cells are confronted with nutrient deprivation and hypoxia. Here, we investigate the roles of autophagy and metabolism in PaCa cell adaptation to environmental stresses, amino acid (AA) depletion, and hypoxia. It is known that in healthy cells, basal autophagy is at a low level, but it is greatly activated by environmental stresses. By contrast, we find that in PaCa cells, basal autophagic activity is relatively high, but AA depletion and hypoxia activate autophagy only weakly or not at all, due to their failure to inhibit mechanistic target of rapamycin. Basal, but not stress-induced, autophagy is necessary for PaCa cell proliferation, and AA supply is even more critical to maintain PaCa cell growth. To gain insight into the underlying mechanisms, we analyzed the effects of autophagy inhibition and AA depletion on PaCa cell metabolism. PaCa cells display mixed oxidative/glycolytic metabolism, with oxidative phosphorylation (OXPHOS) predominant. Both autophagy inhibition and AA depletion dramatically decreased OXPHOS; furthermore, pharmacologic inhibitors of OXPHOS suppressed PaCa cell proliferation. The data indicate that the maintenance of OXPHOS is a key mechanism through which autophagy and AA supply support PaCa cell growth. We find that the expression of oncogenic activation mutation in GTPase Kras markedly promotes basal autophagy and stimulates OXPHOS through an autophagy-dependent mechanism. The results suggest that approaches aimed to suppress OXPHOS, particularly through limiting AA supply, could be beneficial in treating PDAC.
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.