The DOI matches its Crossref record; 48 of the 49 references it cites were found in a registry or an index.
Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism
Open accessAbstract
Activation of cellular stress response pathways to maintain metabolic homeostasis is emerging as a critical growth and survival mechanism in many cancers. The pathogenesis of pancreatic ductal adenocarcinoma (PDA) requires high levels of autophagy, a conserved self-degradative process. However, the regulatory circuits that activate autophagy and reprogram PDA cell metabolism are unknown. Here we show that autophagy induction in PDA occurs as part of a broader transcriptional program that coordinates activation of lysosome biogenesis and function, and nutrient scavenging, mediated by the MiT/TFE family of transcription factors. In human PDA cells, the MiT/TFE proteins--MITF, TFE3 and TFEB--are decoupled from regulatory mechanisms that control their cytoplasmic retention. Increased nuclear import in turn drives the expression of a coherent network of genes that induce high levels of lysosomal catabolic function essential for PDA growth. Unbiased global metabolite profiling reveals that MiT/TFE-dependent autophagy-lysosome activation is specifically required to maintain intracellular amino acid pools. These results identify the MiT/TFE proteins as master regulators of metabolic reprogramming in pancreatic cancer and demonstrate that transcriptional activation of clearance pathways converging on the lysosome is a novel hallmark of aggressive malignancy.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“recent studies have shown that the use of DON or analogs in murine PDAC models also appear to have immunomodulatory effects204,205”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [205]
In the citing paper
“FOXO transcription factors, especially FOXO1 and FOXO3, also play critical roles in the regulation of autophagy gene expression [660, 913, 978].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [978]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Zehorai, E., & Seger, R. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00799-13 · Cited by 34
RetractedSystematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351
Eng, J. K., McCormack, A. L., & Yates, J. R. (1994) · Journal of the American Society for Mass Spectrometry · doi:10.1016/1044-0305(94)80016-2 · Cited by 6,484
Autophagy regulates lipid metabolism
Singh, R., Kaushik, S., Wang, Y., Xiang, Y., Novak, I., Komatsu, M., Tanaka, K., Cuervo, A. M., & Czaja, M. J. (2009) · Nature · doi:10.1038/nature07976 · Cited by 3,975
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969
mTOR: from growth signal integration to cancer, diabetes and ageing
Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
Self-citationElias, J. E., & Gygi, S. P. (2007) · Nature Methods · doi:10.1038/nmeth1019 · Cited by 3,925
Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila
Moy, R. H., & Cherry, S. R. (2013) · Journal of Innate Immunity · doi:10.1159/000350326 · Cited by 3,551
Autophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506
Flagged first, then by citations
1 of the 49 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- Commisso, C. et al. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497, 633–637 (2013) · DOI · Paper page
- Settembre, C. et al. TFEB links autophagy to lysosomal biogenesis. Science 332, 1429–1433 (2011) · DOI · Paper page
- Ballabio, A. & Gieselmann, V. Lysosomal disorders: from storage to cellular damage. Biochim. Biophys. Acta 1793, 684–696 (2009) · DOI · Paper page
- Ting, L., Rad, R., Gygi, S. P. & Haas, W. MS3 eliminates ratio distortion in isobaric multiplexed quantitative proteomics. Nature Methods 8, 937–940 (2011) · DOI · Paper page
Cited by
Sorted by citations
Items 801–801 of 801
Transcriptional control of autophagy: mechanisms, dynamics, and pharmacological modulation
Qin, W., Yang, L., Deng, X., Yuan, W., Guo, D., Xiao, S., Zhang, R., Zhang, Q., Chen, X., Zhou, C., et al. (2026) · Autophagy · doi:10.1080/15548627.2026.2753996
Metadata
- Authors
- Perera, R. M., Stoykova, S., Nicolay, B. N., Ross, K. N., Fitamant, J., Boukhali, M., Lengrand, J., Deshpande, V., Selig, M. K., Ferrone, C. R., Settleman, J., Stephanopoulos, G., Dyson, N. J., Zoncu, R., Ramaswamy, S., Haas, W., & Bardeesy, N.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Massachusetts Institute of Technology (US)
- University of California, Berkeley (US)
- Corresponding author
- Bardeesy, Nabeel
- ORCID
- Venue
- Nature
- Published
- 2015-07-13
- Volume
- 524
- Issue
- 7565
- Pages
- 361-365
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5086585
- OpenAlex
- W1678795445
- Cited by
- 799
- References
- 49
- Citations by year
- 2026: 42 · 2025: 59 · 2024: 64 · 2023: 62 · 2022: 84 · 2021: 107 · 2020: 85 · 2019: 76 · 2018: 77 · 2017: 65 · 2016: 63 · 2015: 13
- FWCI
- 57.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- PMC
- Funders
- Hirshberg Foundation for Pancreatic Cancer Research
- National Institutes of Health (P50CA1270003)
- National Cancer Institute (P50CA127003, P50CA1270003, R01CA133557, DP2CA195761, P01CA117969)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- autophagy, lysosomal biogenesis, pancreatic ductal adenocarcinoma, cancer metabolism, metabolic reprogramming, TFEB, TFE3, MITF, nuclear import, amino acid metabolism, cellular stress response, lysosomal catabolism
- MeSH terms
- Amino Acids, Animals, Autophagy, Energy Metabolism, Female, Homeostasis, Humans, Lysosomes, Neoplasm Transplantation, Pancreatic Neoplasms, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Neoplastic, Carcinoma, Pancreatic Ductal, Active Transport, Cell Nucleus, Cell Line, Tumor, Mice, Microphthalmia-Associated Transcription Factor, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Heterografts
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
