Development of new therapeutics targeting the nfkb pathway and studying the protein protein interaction in melanoma

Abstract

Metastatic melanoma is a type of cancer which aggressively attacks the skin tissues. newlineMelanoma is considered metastatic when it quickly moves to a second site in the body from newlinethe primary site. Although it is a rare form of skin cancer, the progressive form of the cancer newlineis very difficult to treat as it has high metastatic ability which makes it fatal. Patients newlinesuffering from metastatic melanoma are known to have low life expectancies. One of the newlineessential steps which help in the spreading of cancer is the degradation of basement newlinemembranes and extracellular matrix. Matrix metalloproteinases (MMPs) which belong to the newlinemulti-gene family of zinc-dependent endopeptidases are known to be involved in the newlinedegradation of extracellular matrix and basal membrane components. Various MMPs are newlineknown to be over-expressed in melanoma cells, one of which is MMP9. One of the proteins newlinewhich induce MMP9 expression is Basigin (BSG) or CD147. Basigin belongs to the newlineimmunoglobulin superfamily and is also known as EMMPRIN (extracellular matrix newlinemetalloproteinase inducer). As the name implies it is involved in the induction of MMPs. newlineApart from MMP induction, BSG is also involved in VEGF promotion and hyaluronan newlineproduction. The protein structure of BSG consists of an N-terminal immunoglobulin (Ig)-like newlinedomain followed by a transmembrane (TM) domain and a C-terminal intracellular domain. newlineThe TM domain is a stretch of ~23 hydrophobic amino acids which is known to be much newlineconserved among species. newline