ArticleOncogene2006
Hypoxia selects for high-metastatic Lewis lung carcinoma cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors.
Article in Oncogene, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Endoplasmic reticulum stress mediates the myeloid-derived immune suppression associated with cancer and infectious disease.Journal of translational medicine · 2023Review
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- Noninvasive evaluation of hypoxia in rabbit VX2 lung transplant tumors using spectral CT parameters and texture analysis.Japanese journal of radiology · 2022Article
- Article
- Role of hypoxia in cancer therapy by regulating the tumor microenvironment.Molecular cancer · 2019Review
- Article
- Phosphorylated eIF2α predicts disease-free survival in triple-negative breast cancer patients.Scientific reports · 2017Article
- The role of the oncofetal H19 lncRNA in tumor metastasis: orchestrating the EMT-MET decision.Oncotarget · 2016Review
- Interleukin-33 enhances programmed oncosis of ST2L-positive low-metastatic cells in the tumour microenvironment of lung cancer.Cell death & disease · 2016Article
- Dendrofalconerol A sensitizes anoikis and inhibits migration in lung cancer cells.Journal of natural medicines · 2015Article
- Translational regulator eIF2α in tumor.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Review
- Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response.The British journal of radiology · 2014Review
- Cross-talk between HIF and p53 as mediators of molecular responses to physiological and genotoxic stresses.Molecular cancer · 2013Review
- Attenuation of reactive oxygen species by antioxidants suppresses hypoxia-induced epithelial-mesenchymal transition and metastasis of pancreatic cancer cells.Clinical & experimental metastasis · 2013Article
- Regulation of metastasis; mitochondrial DNA mutations have appeared on stage.Journal of bioenergetics and biomembranes · 2012Review
- Article
- Reciprocal influence of the p53 and the hypoxic pathways.Cell death & disease · 2011Review
- Hypoxia-induced autophagic response is associated with aggressive phenotype and elevated incidence of metastasis in orthotopic immunocompetent murine models of head and neck squamous cell carcinomas (HNSCC).Experimental and molecular pathology · 2011Article
- Reactive oxygen species-generating mitochondrial DNA mutation up-regulates hypoxia-inducible factor-1alpha gene transcription via phosphatidylinositol 3-kinase-Akt/protein kinase C/histone deacetylase pathway.The Journal of biological chemistry · 2009Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low oxygen tension (hypoxia) is a common feature of solid tumors and stimulates the expressions of a variety of genes including those related to angiogenesis, apoptosis and endoplasmic reticulum (ER) stress response. Here we show a close correlation between metastatic potential and the resistance to hypoxia- and ER stress-induced apoptosis among the cell lines with differing metastatic potential derived from Lewis lung carcinoma. An apoptosis-specific expression profiling and immunoblot analyses revealed that the expression of antiapoptotic Mcl-1 increased as the resistance to apoptosis increased. Downregulation of the Mcl-1 expression in the high-metastatic cells by Mcl-1 small interfering RNA increased the sensitivity to hypoxia-induced apoptosis and decreased the metastatic ability. The hypoxia-induced apoptosis was not associated with p53 accumulation, although at present it is not possible to conclude that apoptosis-induced apoptosis is p53-independent. There was no correlation between the expression levels of ER stress-response proteins GADD153, GRP78 and ORP150 and the resistance to hypoxia or ER stresses. In vitro, small numbers of the high-metastatic cells overtook the low-metastatic cells after exposure to several rounds of hypoxia and reoxygenation. In solid tumors initially established from equal mixtures, the proportion of the high-metastatic cells to low-metastatic cells was significantly higher in hypoxic areas. Moreover, the high-metastatic cells were overtaking the low-metastatic cells in some of the tumors. Thus, tumor hypoxia and ER stress may provide a physiological selective pressure for the expansion of the high-metastatic cells overexpressing Mcl-1 and exhibiting reduced apoptotic potential in solid tumors.
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