ArticlePloS one2012
Survival of cancer stem cells under hypoxia and serum depletion via decrease in PP2A activity and activation of p38-MAPKAPK2-Hsp27.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Caspase 3 and Cleaved Caspase 3 Expression in Tumorogenesis and Its Correlations with Prognosis in Head and Neck Cancer: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2022Pooled it
- Review
- Protein serine/threonine phosphatases in tumor microenvironment: a vital player and a promising therapeutic target.Theranostics · 2025Review
- Heat shock protein paradigms in cancer progression: future therapeutic perspectives.3 Biotech · 2024Review
- Role of p38 MAP kinase in cancer stem cells and metastasis.Oncogene · 2022Review
- The Role of Hsp27 in Chemotherapy Resistance.Biomedicines · 2022Review
- Targeting NOX4 disrupts the resistance of papillary thyroid carcinoma to chemotherapeutic drugs and lenvatinib.Cell death discovery · 2022Article
- ING4 Promotes Stemness Enrichment of Human Renal Cell Carcinoma Cells Through Inhibiting DUSP4 Expression to Activate the p38 MAPK/type I IFN-Stimulated Gene Signaling Pathway.Frontiers in pharmacology · 2022Article
- Prolonged hypoxia switched on cancer stem cell-like plasticity in HepG2 tumourspheres cultured in serum-free media.In vitro cellular & developmental biology. Animal · 2021Article
- MK2 is a therapeutic target for high-risk multiple myeloma.Haematologica · 2021Article
- CD133 prevents colon cancer cell death induced by serum deprivation through activation of Akt-mediated protein synthesis and inhibition of apoptosis.FEBS open bio · 2021Article
- Pharmacological targeting of the novel β-catenin chromatin-associated kinase p38α in colorectal cancer stem cell tumorspheres and organoids.Cell death & disease · 2021Article
- Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing.Cancers · 2021Review
- Small Heat Shock Proteins in Cancers: Functions and Therapeutic Potential for Cancer Therapy.International journal of molecular sciences · 2020Review
- Review
- A new regulatory mechanism of protein phosphatase 2A activity via SET in acute myeloid leukemia.Blood cancer journal · 2020Article
- Heat shock proteins in cancer stem cell maintenance: A potential therapeutic target?Histology and histopathology · 2020Review
- A Network Pharmacology-Based Study on the Anti-Lung Cancer Effect of Dipsaci Radix.Evidence-based complementary and alternative medicine : eCAM · 2020Article
- PP2A Deficiency Enhances Carcinogenesis of Lgr5Cells · 2019Article
- The mitochondrial deoxyguanosine kinase is required for cancer cell stemness in lung adenocarcinoma.EMBO molecular medicine · 2019Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia and serum depletion are common features of solid tumors that occur upon antiangiogenesis, irradiation and chemotherapy across a wide variety of malignancies. Here we show that tumor cells expressing CD133, a marker for colorectal cancer initiating or stem cells, are enriched and survive under hypoxia and serum depletion conditions, whereas CD133- cells undergo apoptosis. CD133+ tumor cells increase cancer stem cell and epithelial-mesenchymal transition properties. Moreover, via screening a panel of tyrosine and serine/threonine kinase pathways, we identified Hsp27 is constitutively activated in CD133+ cells rather than CD133- cell under hypoxia and serum depletion conditions. However, there was no difference in Hsp27 activation between CD133+ and CD133- cells under normal growth condition. Hsp27 activation, which was mediated by the p38MAPK-MAPKAPK2-Hsp27 pathway, is required for CD133+ cells to inhibit caspase 9 and 3 cleavage. In addition, inhibition of Hsp27 signaling sensitizes CD133+ cells to hypoxia and serum depletion -induced apoptosis. Moreover, the antiapoptotic pathway is also activated in spheroid culture-enriched CD133+ cancer stem cells from a variety of solid tumor cells including lung, brain and oral cancer, suggesting it is a common pathway activated in cancer stem cells from multiple tumor types. Thus, activation of PP2A or inactivation of the p38MAPK-MAPKAPK2-Hsp27 pathway may develop new strategies for cancer therapy by suppression of their TIC population.
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