Melanoma is a type of skin cancer whose incidence has steadily risen particularly in the Caucasianpopulation over the last few decades. In the advanced stages of the disease, melanomas are characterizedwith a high metastatic potential, are extremely refractory to adjuvant therapies like radio- or chemotherapyand are often fatal. These observations underscore the need for developing novel markers indicative ofmetastatic potential and improved treatment modalities targeting the metastatic component of the disease.Melanoma differentiation associated gene-9 (mda-9), also known as syntenin, is an adapter molecule thatplays important roles in diverse cell signaling mechanisms. Recent experiments document an association ofmda-9/syntenin with metastatic cancers. A gradual increase in mda-9/syntenin expression level wasobserved with the progression of melanomas and overexpression of mda-9/syntenin in poorly metastaticbreast or gastric cancer cells increased their invasion and migration properties. Inhibition of mda-9/synteninby siRNA suppressed the invasive phenotype of aggressive melanoma cells indicating that mda-9/synteninmight play a key role in mediating the metastatic process. Based on these findings, the studies in thisproposal will determine the significance of mda-9/syntenin in melanoma progression through the followingspecific aims: i) To correlate changes in mda-9/syntenin expression with different stages of humanmelanoma, ii) To analyze the effect of overexpresssion of mda-9/syntenin on poorly metastatic melanomasand iii) To target mda-9/syntenin as a potential therapeutic intervention for metastatic melanomas.Successful completion of these studies will facilitate the understanding of mda-9/syntenin in melanomametastasis and its development as a diagnostic and/or prognostic tool and a therapeutic target for metastaticmelanomas.Dr. Sarkar qualifies as Category #1 in the Guidelines as a New Investigator with extensiveexpertise in melanoma biology. This P&F study will utilize the services of Cores A, B, C, and D.
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