The Src signaling pathway: a potential target in melanoma and other malignancies.

Although Src was the first oncogene to be discovered as the transforming protein of the Rous sarcoma virus almost three decades ago, the role of Src and the Src family kinases in human oncogenesis is still not completely understood. Recent studies have shown that Src regulates cell adhesion, invasiveness and motility in cancer cells and in tumor vasculature, rather than directly influencing cell replication. The role of the Src family kinases in human cancer is evolving and elevated levels of Src kinase activity have been reported in a number of human cancers in vitro and in vivo. Src expression and activity are increased in melanoma cell lines and in melanoma tumors in vivo. Src can activate STAT3, STAT5 and other downstream targets in melanoma. Src and STAT3 are expressed in their activated forms in both primary and metastatic melanoma in humans, although the expression level is variable. Cumulatively, these data mark Src signaling as attractive therapeutic targets in melanoma. Studies are currently underway with novel Src inhibitors in melanoma and in other tumor types.