Regulation of pro-angiogenic tissue factor expression in hypoxia-induced human lung cancer cells.

摘要: Alternative splicing is a key regulatory mechanism for cellular metabolism controlling cell proliferation and angiogenesis, both of which are crucial processes tumorigenesis under hypoxia. Human cells express two tissue factor (TF) isoforms, alternatively spliced TF (asTF) 'full length' (flTF). flTF the major source thrombogenicity whereas, function soluble asTF, particularly in cancer, widely unknown. In present study, we examined impact alternative on pro-angiogenic potential expression pattern A549 We focused our efforts toward factors, such as Clk1, proliferation-regulating Cyr61. further influence asTF overexpression MCP-1, Cyr61 VEGF, well number properties cells. Notably, found hypoxia to induce factors (Clk1 Clk4) proliferation- angiogenesis-promoting (Cyr61 flTF). also increased tube formation. These effects were mediated by induction Cyr61, MCP-1 integrin α(v)β(3). Taken together, results suggest that lung cancer modulated hypoxic conditions via modulation isoform turn controlled splicing.