Upregulation of autophagy by hypoxia-inducible factor-1α promotes EMT and metastatic ability of CD133+ pancreatic cancer stem-like cells during intermittent hypoxia
Open accessAbstract
Epithelial-to-mesenchymal transition (EMT) facilitates the escape of pancreatic cancer cells from the primary tumor site, which is a key early event in metastasis. In the present study, we examined if intermittent hypoxia facilitates the invasiveness of human pancreatic cancer cell lines (Panc-1 and BxPC-3) by Transwell assay. We used western blotting and flow cytometry analysis to quantify stem-like cells in the migratory cells during intermittent hypoxia in the human pancreatic cancer cells. Under normoxia or intermittent hypoxia, the expression of autophagy-related proteins (LC3-II and Beclin), hypoxia-inducible factor-1α (HIF-1α) and EMT-related markers (E-cadherin, Vimentin and N-cadherin) was examined by western blotting. siRNA and the autophagic inhibitor were used to access the role of HIF-1α and autophagy in promoting metastasis and EMT. Under intermittent hypoxia, pancreatic cancer cells demonstrated enhanced invasive ability and enriched stem-like cells. The migratory cells displayed stem-like cell characteristics and elevated the expression of LC3-II and Beclin-1, HIF-1α, E-cadherin, Vimentin and N-cadherin under intermittent hypoxia conditions. Moreover, enhanced autophagy was induced by the elevated level of HIF-1α. The metastatic ability and EMT of pancreatic cancer stem cells was associated with HIF-1α and autophagy. This novel finding may indicate the specific role of HIF-1α and autophagy in promoting the metastatic ability of pancreatic cancer stem cells. Additionally, it emphasizes the importance of developing therapeutic strategies targeting cancer stem cells and autophagy to reduce metastasis.
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
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?
Downstream effects include conversion to cancer stem cell properties, increased NOX1 subunit of NADPH oxidase, increased monocyte polarization toward a tumor-promoting phenotype, glycolysis, and extracellular matrix remodeling.
“Examples of these downstream effects are conversion to cancer stem cell properties,874 increased NOX1 subunit of NADPH oxidase,875 increased monocyte polarization toward a tumor-promoting phenotype,876 glycolysis,873 and extracellular matrix remodeling.877”
From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [874]
Only the phrase cited to this paper—conversion to cancer stem cell properties—is at issue. In the section on intermittent hypoxia and pancreatic cancer cell migration (page unavailable), the paper reports a larger CD133-positive population, greater sphere formation, and higher stem-cell marker expression under intermittent hypoxia. These findings support enrichment of stem-like properties, but do not establish that non-stem cells converted into cancer stem cells. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn vitro models have shown that cyclical intermittent hypoxia produces changes distinct from sustained hypoxia.
“In vitro models have provided two main findings: (1) CIH results in changes that are distinct from sustained hypoxia;”
From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [874]
The Results section reports changes in pancreatic cancer cells under intermittent hypoxia compared with normoxia. The Discussion distinguishes intermittent hypoxia from permanent low-oxygen exposure, but the study does not compare their cellular effects; it therefore does not establish that the resulting changes are distinct from those under sustained hypoxia. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn vitro models have shown that cyclical intermittent hypoxia produces molecular changes that promote cancer progression or metastases.
“(2) CIH results in molecular changes that promote cancer progression or metastases.”
From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [874]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 34 · Cited by 124
- Authors
- ZHU, H., WANG, D., ZHANG, L., XIE, X., WU, Y., LIU, Y., SHAO, G., & SU, Z.
- Affiliations
- Affiliated Hospital of Jiangsu University (CN)
- Jiangsu University (CN)
- Venue
- Oncology Reports
- Publisher
- Spandidos Publications
- Published
- 2014-07-02
- Volume
- 32
- Issue
- 3
- Pages
- 935-942
- ISSN
- 1021-335X (ISSN-L)
- 1791-2431
- OpenAlex
- W1980339030
- Semantic Scholar
- 54f083e246619e8d943eb9519b6eb803de406981
- Cited by
- 124
- References
- 34
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 6 · 2023: 5 · 2022: 23 · 2021: 14 · 2020: 14 · 2019: 10 · 2018: 12 · 2017: 15 · 2016: 7 · 2015: 10 · 2014: 4
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Oncology Reports (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (11JDG128, 2013T60508, 81101677, 1102129C, 81370084, BK2011487, 2012M511705, 81001319, 10KJB310003)
- Jiangsu University
- Government of Jiangsu Province (1102129C)
- Natural Science Foundation of Jiangsu Province (2012M511705, 10KJB310003, 11JDG128, BK2011487, 1102129C, 81101677, 2013T60508, 81001319, 81370084)
- Natural Science Research of Jiangsu Higher Education Institutions of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- autophagy, hypoxia-inducible factor-1α, epithelial-mesenchymal transition, pancreatic cancer, cancer stem cells, CD133, intermittent hypoxia, metastasis, cell invasion, stem-like cells, LC3-II, Beclin-1, E-cadherin, vimentin, N-cadherin
- MeSH terms
- AC133 Antigen, Autophagy, Cell Movement, Glycoproteins, Humans, Neoplasm Metastasis, Pancreatic Neoplasms, Peptides, Neoplastic Stem Cells, Cell Hypoxia, Antigens, CD, Up-Regulation, Cell Line, Tumor, Hypoxia-Inducible Factor 1, alpha Subunit, Epithelial-Mesenchymal Transition
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
