[Oncogen dependent regulation of the migration and proliferation of human tumor cells]

The high mortality of solid tumors can be attributed to their invasive and metastatic potential that is based on their migration and proliferation. Importantly, growth factor receptor (GF) signaling pathways regulating proliferation and migration are often affected by oncogenic mutations and are important targets for antitumor therapy. We found positive correlation between migration and proliferation in melanoma and lung cancer cells using videomicroscopy, not supporting the "go or grow" hypothesis. Furthermore, the invasion into collagen I matrices from brain tumor spheroids was not impaired upon the inhibition of proliferation. Sensitivity of human melanoma cells towards EGF and FGF2 treatment but not against GF receptor tyrosine kinase inhibitors was oncogenic BRAF or NRAS mutation status dependent. Prenylation inhibition failed to decrease clonogenic growth in BRAF mutant but PTEN wild-type melanoma lines but increased migration in BRAF-mutant cells. In certain mesothelioma cells, activin signaling showed a pro-tumorigenic effect suggesting activin as a valuable candidate for therapeutic interference. In summary, our findings demonstrate that proliferation is neither an obstacle nor a prerequisite for tumor cell invasion. Furthermore, the specific oncogenic mutations may differentially regulate migration and proliferation of tumor cells. Therefore, they are not only therapeutic targets but can also profoundly influence the efficacy of various therapies.