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Consequence of differential activation of Notch signalling in ovarian cancer progression and chemo resistance

Consequence of differential activation of Notch signalling in ovarian cancer progression and chemo resistance

Cellular communication and interactions are critical and essential for the sustenance and progression of complex diseases like cancer. The involvement of peritoneal microenvironment is even more striking with a preponderance of transcoelomic metastasis in epithelial ovarian cancer. Albeit omentum, a fold of inner peritoneum made up of fatty-tissue, is the most common site of ovarian metastasis, there is a heterogeneity in the distribution of metastatic foci indicating a possible underlying modulator in the omental mesothelial cells. Also, there is a potential cell-to-cell interaction that implies a possible involvement of Notch-3, a well-known juxtacrine signalling pathway.

In order to study whether a potential differential activation of Notch-3 in the tumor cells by the heterogeneous ligand expression (Jag-1) in mesothelial cells can lead to further disease progression and altered drug sensitivity, a luciferase-based reporter sensor platform has been developed along with differential cellular clones of jagged-1 mimicking the in vivo scenario. I am also investigating the effect of activated Notch-3 on different cellular phenotypes through functional assays.

Usha Patel

Senior Research Fellow

Souvik Mukherjee

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