Targeting epithelial-mesenchymal transition using glycosylated calcium regulators to inhibit breast cancer progression

Ca2+ is a key inorganic molecule required for a vast majority of cellular functions. Therefore, careful management of Ca2+ dynamics is essential for optimal cell function. We previously identified the role of a glycosylated protein, syndecan-1 (SDC 1), in cytosolic Ca2+ dynamics. SDC 1, a protein that bears glycosaminoglycan chains, is dysregulated in breast cancer.

The functions of SDC1 rely on glycosaminoglycan chains and modifications of the glycosaminoglycan chains. We found that loss of SDC1 from mammary epithelial cells leads to epithelial-to-mesenchymal transition (EMT). EMT is an indispensable process during breast cancer progression, which allows cancer cells to metastasize.

We identified a subset of EMT-promoting transcription factors that are upregulated in SDC1 knockout cells, which is driven by an increase in cellular Ca2+ levels. We hypothesise that Ca2+ changes would induce the expression and activity of EMT-promoting transcription factors. However, the impact of SDC1 mediated Ca2+ on EMT-promoting transcription factors remains unclear.

In this study, we aim to understand how the progressive depletion of SDC1 and changes in glycosaminoglycan-modifying enzymes control Ca2+ dynamics during EMT in breast epithelial cells.

We will use compounds targeting glycosaminoglycan-modifying enzymes to test their potential as targets for Ca2+ management to prevent breast cancer progression.