The proinvasive effect of HGF (left) is amplified by hypoxia (right).
Comoglio/Elsevier
The response appears to be part of a normal program used to create and maintain organs—a process that uses oxygen gradients as one guiding principle. “Mother Nature has given us the invasion program not to promote metastasis but to promote sprouting and branching of epithelial tubes,” says Comoglio.
In hypoxic tumor cells, his team found that binding of hypoxia inducible factor-1 (HIF-1) to two sites in the met promoter-induced expression of the Met tyrosine kinase receptor. This newly abundant Met, after the binding of ubiquitous hepatocyte growth factor (HGF, or scatter factor-1), activates an invasive migration program.
They found that Met levels were...
