Peroxisome proliferator-activated receptor-γ (PPAR-γ) has emerged as one of the most extensively studied transcription factors since its discovery in 1990, highlighting its importance in the etiology and treatment of numerous diseases involving various types of cancer, type 2 diabetes mellitus, autoimmune, dermatological and cardiovascular disorders. Ligands are regarded as the key determinant for the tissue-specific activation of PPAR-γ. However, the mechanism governing this process is merely a contradictory debate which is yet to be systematically researched. Either these receptors get weakly activated by endogenous or natural ligands or leads to a direct over-activation process by synthetic ligands, serving as complete full agonists. Therefore, fine-tuning on the action of PPAR-γ and more subtle modulation can be a rewarding approach which might open new avenues for the treatment of several diseases. In the recent era, researchers have sought to develop safer partial PPAR-γ agonists in order to dodge the toxicity induced by full agonists, akin to a balanced activation. With a particular reference to cancer, this review concentrates on the therapeutic role of partial agonists, especially in cancer treatment. Additionally, a timely examination of their efficacy on various other disease-fate decisions has been also discussed.

Matrix remodeling and invasion of basement membrane are the major determinants of malignant progression. Matrix degrading enzymes play a pivotal role in this process and have been shown to be regulated at multiple levels. Using high metastatic B16F10 and its invasive variant B16BL6 cells, we previously demonstrated that the expression ofβ1,6 branched N-oligosaccharides promotes cellular adhesion on different matrix components which in turn induces secretion of MMP9. The present investigations report that although the two cell lines do not differ in the expression of uPAR, expression of MT1-MMP is significantly higher on B16BL6 cells. Analysis of the transcripts of tissue inhibitors of matrix metalloproteinases (TIMPs) showed that expression of both TIMP1 and TIMP2 correlates negatively with the invasive potential of cells. CD44 andβ1 integrin, the two important receptors involved in motility, were identified to carryβ1,6 branched N-oligosaccharides in an invasive potential dependent manner. However, their glycosylation status did not appear to influence their surface expression. Although glycosylation on CD44 had no effect, that onβ1 integrin significantly affected association ofβ1 integrin with MT1-MMP. The results thus demonstrate that the cancer cells use multiple mechanisms for degradation of matrix in a controlled manner to couple it with movement for effective invasion.