Executive Summary : | Cancer populations are inherently heterogeneous, with evidence showing this in various types of tumors, including breast, lung, and brain cancer. This heterogeneity is crucial for cancer growth, metastasis, and drug resistance development. Cancer cell glycocalyx, which is denser and over-extended, acts as an extracellular barrier, preventing pathogens and other molecules from entering the cell. Mucin-1 (MUC1), a major glycoprotein in breast cancer, is over-expressed and hyper-glycosylated, enabling it to entrap growth factors and enhance cell proliferation. The tumor-microenvironment causes sequential cleavage of MUC1, leading to its internalization and nuclear localization. Within the nucleus, it can act as a transcriptional factor, leading to increased cell division, drug resistance, cancer stemness, and invasion. This project aims to study glycocalyx heterogeneity in the context of Mucin-1 and its association with drug sensitivity. Quantitative measurements of MUC1 levels will be conducted in breast cancer cell lines and patient samples before and after chemotherapeutic drug administration. The cells will be sorted into sub-populations based on MUC1 heterogeneity using flow-cytometry, and drug sensitivity will be studied. The study will help to understand the importance of Mucin-1 signaling and barrier function in maintaining cancer stemness, metastasis, and drug resistance. |