Is STAT5 activity a key factor in prostate cancer metastasis?
Posted May 20 2010 12:00am
STAT5 refers to a pair of signaling proteins (STAT5A and STAT5B) that researchers had previously thought were involved in the growth of established prostate cancer tumors. However, a new paper in Endocrine-Related Cancer suggests that STAT5 may have a critical role in the process of prostate cancer metastasis.
The “signal transducers and activator of transcription” proteins ( STAT proteins ) regulate many aspects of cell growth, survival and differentiation. It has previously been shown that STAT5 protein is activated in 61 percent of distant metastases in patients with prostate cancer. Indeed, as long ago as 2005, Nevalainen and colleagues had suggested that testing for an activated STAT5 protein in prostate tumor tissue could effective predict which men might have a form of prostate cancer that would become more aggressive and life threatening.
Now, building on this earlier research, Gu et al. have shown, among other things, that:
Active STAT5 increased the formation of prostate cancer metastases 11-fold in an experimental metastases assay in a mouse model.
Active STAT5 promoted migration and invasion of prostate cancer cells, and induced rearrangement of the microtubule network.
Active STAT5 expression stimulated heterotypic adhesion of prostate cancer cells to endothelial cells.
Activation of STAT5 and STAT5-induced binding of prostate cancer cells to endothelial cells could be decreased by inhibition of Src (but not by inhibition of Jak2).
21 percent of the genes regulated by STAT5 in prostate cancer cells were related to metastases; another 7.9 percent were related to proliferation and 3.9 percent to apoptosis.
This new research appears to offer distinct evidence of the potential importance of STAT5 in the induction of metastatic behavior of human prostate cancer cells. If these new data can be substantiated, then STAT5 may be prove to be a new therapeutic target for patients with progressive forms of prostate cancer. In other words, it is possible that inhibition of STAT5 may be able to delay or significantly reduce the probability of metastasis of prostate cancer in patients who have bichemical failure after first-line therapy.