ArticleBreast cancer research : BCR2013
Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response.
Article in Breast cancer research : BCR, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
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136 citing papers in PubMed, 1 synthesis or guideline pooled it, 226 citations in OpenAlex.
- Links between the unfolded protein response and the DNA damage response in hypoxia: a systematic review.Biochemical Society transactions · 2021Pooled it
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- Bioactive metallic nanoparticles for synergistic cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- PERK-Olating Through Cancer: A Brew of Cellular Decisions.Biomolecules · 2025Review
- Development of a Novel Lysosomal Gene-based Prognostic Panel and Uncovering EIF4EBP1 as a Biomarker for Breast Cancer.Current genomics · 2025Article
- UGT1A7 altered HER2-positive breast cancer response to trastuzumab by affecting epithelial-to-mesenchymal transition: A potential biomarker to identify patients resistant to trastuzumab treatment.Cancer gene therapy · 2024Article
- A covalent creatine kinase inhibitor ablates glioblastoma migration and sensitizes tumors to oxidative stress.Scientific reports · 2024Article
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- Triggering of endoplasmic reticulum stress via ATF4-SPHK1 signaling promotes glioblastoma invasion and chemoresistance.Cell death & disease · 2024Article
- Mammalian integrated stress responses in stressed organelles and their functions.Acta pharmacologica Sinica · 2024Review
- Impact of Obesity-Related Endoplasmic Reticulum Stress on Cancer and Associated Molecular Targets.Biomedicines · 2024Review
- Ratiometric near-infrared fluorescent probe for nitroreductase activity enables 3D imaging of hypoxic cells within intact tumor spheroids.Chemical science · 2024Article
- Curcumin inhibits the development of colorectal cancer via regulating the USP4/LAMP3 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Rapid prototyping of PMMA-based microfluidic spheroid-on-a-chip models using micromilling and vapour-assisted thermal bonding.Scientific reports · 2024Article
- A pan-cancer analysis of prognostic significance and immunological role of lysosomal-associated membrane protein 3.Journal of cellular and molecular medicine · 2024Article
- LAMP3 is a potent uterine corpus endometrial carcinoma prognostic biomarker associated with immune behavior.Aging · 2024Article
- ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Oestrogen Receptor-Positive Breast Cancer.Pathobiology : journal of immunopathology, molecular and cellular biology · 2024Article
- Staining Hypoxic Areas of Frozen and FFPE Tissue Sections with Hypoxyprobe™.Methods in molecular biology (Clifton, N.J.) · 2024Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe hypoxia-inducible factor (HIF)-1 pathway can stimulate tumor cell migration and metastasis. Furthermore, hypoxic tumors are associated with a poor prognosis. Besides the HIF-1 pathway, the unfolded protein response (UPR) is also induced by hypoxic conditions. The PKR-like ER kinase (PERK)/activating transcription factor 4 (ATF4)-arm of the UPR induces expression of lysosomal-associated membrane protein 3 (LAMP3), a factor that has been linked to metastasis and poor prognosis in solid tumors. In this study the role of UPR-induced LAMP3 in hypoxia-mediated migration of breast cancer cells was examined.
methodsA number of in vitro metastasis models were used to study the migration and invasion of MDA-MB-231 breast cancer cells under hypoxic conditions. PERK, ATF4 and their downstream factor LAMP3 were knocked down to examine their role in cell migration. In addition, multicellular tumor spheroids were used to study the involvement of the tumor microenvironment in invasion.
resultsUsing transwell assays, migration of different breast cancer cell lines was assessed. A direct correlation was found between cell migration and baseline LAMP3 expression. Furthermore, moderate hypoxia (1% O2) was found to be optimal in stimulating migration of MDA-MB-231 cells. siRNA mediated knockdown of PERK, ATF4 and LAMP3 reduced migration of cells under these conditions. Using gap closure assays, similar results were found. In a three-dimensional invasion assay into collagen, LAMP3 knockdown cells showed a diminished capacity to invade compared to control cells when collectively grown in multicellular spheroids.
conclusionsThus, the PERK/ATF4/LAMP3-arm of the UPR is an additional pathway mediating hypoxia-induced breast cancer cell migration.
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