Migration of renal tumor cells depends on dephosphorylation of Shc by PTEN.

The tumor suppressor PTEN is a phosphatase using FAK and Shc as direct substrates, and Akt as a key effector via PIP3. PTEN regulates cell migration and may influence metastases. We quantified PTEN in 135 clear cell renal cell carcinomas (ccRCC) by Western blot analysis and found statistically significant lower PTEN expression in patients who died, usually caused by metastases, within 5 years after surgery, compared to those surviving this time period. In athymic mice, PTEN transfected 786-O cells were injected into the tail vein and metastatic load of the lungs was quantified. We observed a strongly reduced metastatic load after PTEN transfection. For analyses of the PTEN activities, trans…