ArticleOncogene2016
Hypoxia-induced oxidative stress promotes MUC4 degradation via autophagy to enhance pancreatic cancer cells survival.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Tumor microenvironment-specific nanomedicine: from biology-driven to multi-omics-guided precision engineering.Journal of hematology & oncology · 2026Review
- Locoregional Therapies and Remodeling of Tumor Microenvironment in Pancreatic Cancer.International journal of molecular sciences · 2023Review
- Review
- Hypoxia-induced oxidative stress promotes therapy resistance via upregulation of heme oxygenase-1 in multiple myeloma.Cancer medicine · 2023Article
- High expression of hypoxia-inducible factor 1-alpha predicts poor prognosis in pancreatic ductal adenocarcinoma: a meta-analysis and database validation protocol.Translational cancer research · 2022Article
- Article
- Autophagy-Dependent Ferroptosis-Related Signature is Closely Associated with the Prognosis and Tumor Immune Escape of Patients with Glioma.International journal of general medicine · 2022Article
- The response of three-dimensional pancreatic alpha and beta cell co-cultures to oxidative stress.PloS one · 2022Article
- Oxygen and metabolic reprogramming in the tumor microenvironment influences metastasis homing.Cancer biology & therapy · 2021Review
- Proteogenomics of non-small cell lung cancer reveals molecular subtypes associated with specific therapeutic targets and immune evasion mechanisms.Nature cancer · 2021Article
- Regulation and function of autophagy in pancreatic cancer.Autophagy · 2021Review
- Modulation of cell physiology under hypoxia in pancreatic cancer.World journal of gastroenterology · 2021Review
- A 4-gene-based hypoxia signature is associated with tumor immune microenvironment and predicts the prognosis of pancreatic cancer patients.World journal of surgical oncology · 2021Article
- Targeting hypoxic tumor microenvironment in pancreatic cancer.Journal of hematology & oncology · 2021Review
- Article
- STIM1 overexpression in hypoxia microenvironment contributes to pancreatic carcinoma progression.Cancer biology & medicine · 2019Article
- Study of oxygen tension variation within live tumor spheroids using microfluidic devices and multi-photon laser scanning microscopy.RSC advances · 2018Article
- Novel oncogene COPS3 interacts with Beclin1 and Raf-1 to regulate metastasis of osteosarcoma through autophagy.Journal of experimental & clinical cancer research : CR · 2018Article
- Notch signaling molecule is involved in the invasion of MiaPaCa2 cells induced by CoCl2 via regulating epithelial‑mesenchymal transition.Molecular medicine reports · 2018Article
- ATD: a comprehensive bioinformatics resource for deciphering the association of autophagy and diseases.Database : the journal of biological databases and curation · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic cancer (PC) and associated pre-neoplastic lesions have been reported to be hypoxic, primarily due to hypovascular nature of PC. Though the presence of hypoxia under cancerous condition has been associated with the overexpression of oncogenic proteins (MUC1), multiple emerging reports have also indicated the growth inhibitory effects of hypoxia. In spite of being recognized as the top-most differentially expressed and established oncogenic protein in PC, MUC4 regulation in terms of micro-environmental stress has not been determined. Herein, for the first time, we are reporting that MUC4 protein stability is drastically affected in PC, under hypoxic condition in a hypoxia inducible factor 1α (HIF-1α)-independent manner. Mechanistically, we have demonstrated that hypoxia-mediated induction of reactive oxygen species (ROS) promotes autophagy by inhibiting pAkt/mTORC1 pathway, one of the central regulators of autophagy. Immunohistofluorescence analyses revealed significant negative correlation (P-value=0.017) between 8-hydroxy guanosine (8-OHG) and MUC4 in primary pancreatic tumors (n=25). Moreover, we found pronounced colocalization between MUC4 and LAMP1/LC3 (microtubule-associated protein 1A/1B-light chain 3) in PC tissues and also observed their negative relationship in their expression pattern, suggesting that areas with high autophagy rate had less MUC4 expression. We also found that hypoxia and ROS have negative impact on overall cell growth and viability, which was partially, though significantly (P<0.05), rescued in the presence of MUC4. Altogether, hypoxia-mediated oxidative stress induces autophagy in PC, leading to the MUC4 degradation to enhance survival, possibly by offering required metabolites to stressed cells.
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