Executive Summary : | Breast cancer (BC) is the most common cancer in India, with 25.8 patients suffering and 12.7 dying from it per 100,000 women. Understanding the disease progression is crucial for successful therapeutic intervention. One major stage in cancer progression is metastasis, where tumor cells leave their original site and recolonize into new tissue. In metastatic BC, prognosis is generally poor, so stopping/controlling metastasis is a proposed therapeutic intervention. Directed migration plays a crucial role in metastasis, and a thorough understanding of cellular migration in BC is imperative. The gradient in substrate rigidity is known as a cue for directed migration, and adherent cells migrate from soft to rigid substrate, a phenomenon known as Durotaxis. However, viscoelastic tissues are insufficient to describe the rheological complexity of living systems. In malignant conditions, both the storage and loss modulus (G”) of the breast change significantly. The present proposal aims to explore Durotaxis and Viscotaxis in BC with non-invasive (MCF7) and invasive (MDA-MB-231) breast cancer cells. The study will focus on understanding the difference between MCF7 and MDA-MB-231, elucidating the molecular mechanism, investigating the relative importance of these two gradients, and modeling migration in response to combinatorial cues of G' and G”. The proposed work will provide fundamental understanding about migration in breast cancer and help find new therapeutic targets, as well as apply insights gained for other pathophysiological conditions that involve cellular migration. |