Sandra Cascio, PhD
Campus: 200 Lothrop St
Office: BSTWR E1000-16B - 18A
Pittsburgh, PA 15261
- PhD, University of Palermo
- Research Assistant Professor
My research interests are in elucidating the molecular mechanisms that characterize the immune microenvironment of solid tumors (breast, colon and ovarian cancer) with a particular focus on the cancer and inflammation network. We are currently carrying out two areas of investigation:
1. Characterizing the abnormal hypoglycosylated form of the epithelial mucin MUC1 as a link between cancer and inflammation
The tumor antigen and oncoprotein MUC1 is overexpressed and hypoglycosylated in chronic inflammation and adenocarcinomas. We study the ability of the hypoglycosylated MUC1, in association with NF-kB, p65, to regulate pro-inflammatory cytokine gene expression in epithelial cancer cells leading to increased inflammation and tumor promotion. This abnormal form of MUC1 also induces histone post-translational modifications involved in chromatin remodeling and resulting in an enhanced pro-inflammatory cytokine transcription.
We also analyze whether MUC1 glycosylation change is involved in the recruitment of inflammatory cells into the tumor microenvironment with particular focus on the macrophage M1/M2 polarization.
2. MUC1/CIN85 complex in cancer progression and metastasis
Metastatic spread of cancer is responsible for most cancer deaths. We identified CIN85 (Cbl-interacting protein 85 KDa), as a key binding partner of hypoglycosylated MUC1. Co-localization of MUC1 and CIN85 on invadopodia-like structures enhances invasion and migration of epithelial cancer cells. We are in process of testing novel drug compounds that, based on our recent results, target the CIN85/MUC1 complex. Our goals is to identify those that might be developed for anti-metastatic therapy.
Cascio S, Xue J, Faylo, J, Sciurba J and Finn OJ, A critical role of EzH2 in the MUC1-mediated induction of pro-inflammatory cytokines in colitis-associated tumorigenesis. Submitted
Cascio S and O Finn. Complex of MUC1, CIN85 and Cbl in Colon Cancer Progression and Metastasis. Cancers 2015 March; 7(1): 342–352.
Cascio S, Farkas AM, Hughey RP, Finn OJ. Altered glycosylation of MUC1 influences its association with CIN85: the role of this novel complex in cancer cell invasion and migration. Oncotarget 2013 Oct;4(10):1686-97.
Cascio S, Zhang L, Finn OJ. MUC1 protein expression in tumor cells regulates transcription of proinflammatory cytokines by forming a complex with nuclear factor-kB p65 and binding to cytokine promoters: importance of extracellular domain. J Biol Chem. 2011 Dec 9;286 (49):42248-56. (Selected by Faculty 1000).\
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