Caveolin-1 promotes gastric cancer progression by up-regulating epithelial to mesenchymal transition by crosstalk of signalling mechanisms under hypoxic condition
Autor: | Devaraj Halagowder, Mohammed Ali, Niranjali Devaraj Sivasithamparam, Anbarasu Kannan, Shyama Subramaniam, Arunkumar Krishnan |
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Rok vydání: | 2014 |
Předmět: |
Male
Cancer Research Epithelial-Mesenchymal Transition Caveolin 1 Vimentin Cell Growth Processes Stomach Neoplasms Cell Line Tumor Humans Epidermal growth factor receptor Epithelial–mesenchymal transition STAT3 Neoplasm Staging biology Cell growth Middle Aged Hypoxia-Inducible Factor 1 alpha Subunit Immunohistochemistry Cell Hypoxia Up-Regulation Crosstalk (biology) Oncology Biochemistry Disease Progression Cancer research biology.protein Female Signal Transduction Transforming growth factor |
Zdroj: | European Journal of Cancer. 50:204-215 |
ISSN: | 0959-8049 |
DOI: | 10.1016/j.ejca.2013.08.016 |
Popis: | Gastric cancer is the second most fatal common form of cancer. The crosstalk among signalling pathways that results in the acceleration of epithelial to mesenchymal transition (EMT) plays a pivotal role in the molecular mechanism of gastric carcinogenesis. To understand the role of caveolin-1 (Cav-1), the expression pattern was studied in human gastric adenocarcinoma tissues and also in AGS and KATO III cell lines. Here, we show that during hypoxic condition, the increase in the levels of hypoxia-inducible factor-1α (HIF-1α) results in a significant decrease in the expression of caveolin-1 which is regulated by heat shock protein 90 (HSP90). The reduced levels of Cav-1 correlated with the increased epidermal growth factor receptor (EGFR) activation resulting in the significant activation of its downstream target STAT3. Accumulation of pSTAT3 in the nucleus results in the decreased expression of E-cadherin and increased expression of mesenchymal markers (Slug, α-SMA, N-cadherin and vimentin). Crosstalk of EGFR and transforming growth factor β (TGF-β) signalling with Wnt signalling enhances cell proliferation, cell survival and upregulates EMT. There was no significant alteration in the expression of epithelial and mesenchymal molecules in both the cell lines studied. Thus, we provide evidence that Cav-1 was modulated by HSP90 and functions as a crucial regulator of EMT in gastric cancer. |
Databáze: | OpenAIRE |
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