arious tumor suppressor genes in regulation of cancer progression and their possible role in cancer therapeutics is under intense investigation. Semaphorins have been originally known as a large family of evolutionary conserved ” axonal guidance molecules. The role of 12098599” semaphorins in various physiological as well as pathophysiological processes including cell migration, regulation of immune response, angiogenesis and cancer have recently been studied. Among various semaphorins, selected members of semaphorin 3 family are involved in suppression of tumor progression and have been considered as potent tumor suppressors. Loss of expressions of Sema 3B and Sema 3F gene have been shown to associate with lung cancer progression. On the other hand, overexpression of these molecules inhibits tumor cell proliferation and in vivo tumor growth. Moreover, Semaphorin 3A, another member of this family is shown to inhibit angiogenesis and acts as tumor suppressor. Sema 3A is originally described as a secretory protein with potent axonal repulsive activity. Polleux et al have identified the chemoattractive effect of Sema 3A on cortical apical dendrites and 
shown that Sema 3A acts as a crucial regulatory molecule for ABT-578 neuronal development. However, Serini et al have observed a significant vascular defect in Sema 3A null mice. In this study, we have deciphered the function of Sema 3A beyond brain, and demonstrated that this protein could play an important role in melanoma growth. Knockdown of endogenous Sema 3A significantly induce in vitro migration of human breast cancer cell and indicated that Sema 3A may act as a potent tumor suppressor. Overexpression of Sema 3A attenuates invasion and matrigel adhesion of human prostate cancer cells. Moreover, loss of Sema 3A inhibitory loop in hormone-refractory human prostatic cancer has been recently identified by tissue microarray analysis Semaphorin 3A Attenuates Melanoma Progression and further suggested that deregulation of Sema 3A pathway could be an important therapeutic target for prostate cancer progression. Furthermore, overexpression of Sema 3A significantly suppresses in vivo breast tumor growth in mouse xenograft model. However, the function of Sema 3A in regulation of melanoma progression is not well studied, and yet to be a field of intense investigation. Angiogenesis, or formation of new blood vessel from the existing one has been considered as the most important step during tumor progression. Current advancement in cancer research has shown that targeting angiogenic pathways could be a more rational and promising anti-cancer therapeutic approach. To date, vascular endothelial growth factor is considered as one of the most potent angiogenic factor that governs tumor angiogenesis. Interaction between VEGF and one of its co-receptor neuropilin 1 is known to play an important role in tumor angiogenesis and therefore blocking their interaction could be a rational anti-angiogenic therapeutic approach for cancer treatment. Moreover, NRP1 has been identified as one of the co-receptors of Sema 3A. Miao et al. have shown that Sema 3A and/or VEGF act as competitive ligand for binding to NRP1 and described that Sema 3A can attenuate VEGF-induced endothelial cell motility. Thus, Sema 3A could act as a potent inhibitor of tumor angiogenesis by disrupting the interaction between VEGF and NRP1. Very recently, using transgenic mice model, Maione et al. have shown that Sema 3A acts as an endogenous angiogenesis inhibi