Study Outlines Importance of the Vav1 Oncogene in Cancer Development

The Vav1 oncogene has been found to play a much broader role in the development of various types of cancer than previously had been thought.

Cancer results from the interaction of multiple abnormalities including activation of dominant oncogenes and up regulation of signal transduction pathways. Identification of the genes involved in malignant transformation is a requirement for understanding cancer and improving its diagnosis and treatment.

Many of the genes that have been implicated in cancer are mutant or aberrantly expressed versions of genes that are important mediators of the normal growth that occurs during development. Investigators at the Hebrew University of Jerusalem (Israel) recently reported on an important example of this, Vav1. This oncogene encodes for a cytoplasmic signal transducer protein.

Physiological expression of Vav1 is restricted to the hematopoietic system, where its best-known function is as a GDP/GTP nucleotide exchange factor for Rho/Rac GTPases, an activity strictly controlled by tyrosine phosphorylation. Vav1 was shown to regulate cytoskeletal rearrangement during activation of hematopoietic cells. Vav1 can also mediate other cellular functions including activation of the JNK, ERK, Ras, NF-kappaB, and NFAT pathways, in addition to association with numerous adapter proteins such as Shc, NCK, SLP-76, GRB2, and Crk. Although the oncogenic form of Vav1 has not been detected in clinical human tumors, its wild-type form has recently been implicated in mammalian malignancies such as neuroblastoma, melanoma, pancreatic tumors, and B-cell chronic lymphocytic leukemia.

A paper that was published by the Hebrew University investigators in the May 10, 2010, online edition of the Journal of Biological Chemistry further elucidated the role of Vav1 and revealed that it was expressed in 44% of malignant human lung cancer-tissue samples that were studied.

These findings led the investigators to conclude that, "Since Vav1 has now been shown to play a role in the process of abnormal tissue growth in several human cancers, it has become an even more highly important potential therapeutic target for cancer therapy.”

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