Tumor suppressor function of Rab25 in triple-negative breast cancer.

Rab proteins are a group of ubiquitously expressed proteins that are responsible for intracellular transport of vesicles. Recent evidence has shown that certain Rab proteins are involved in the pathogenesis of cancer. We have recently shown that Rab25 is lost in a large fraction of breast cancer samples, particularly those derived from hormonally insensitive tumors. We have further investigated the role of Rab25 by re-expressing Rab25 in tumorigenic cell lines and measuring the impact on tumor formation as well as on various molecular pathways through PCR array analysis. In vivo tumor growth of cell lines with re-expressed Rab25 was markedly suppressed. Our data suggest that Rab25 acts through multiple pathways to enhance apoptosis and to suppress angiogenesis and invasion by modulating VEGF-A and VEGFR-1 expression. These findings suggest that Rab25 represents a novel class of cellular modulators that can influence both tumor initiation and the progression of the established tumors, thus ultimately affecting the biology of the malignant disease.