As a translational expansion of our bench-side discoveries, we are exploring how Agrin could serve as a prognostic marker for cancers.

Figure from a scientific research study
Oncogenic communications by Agrin

As a potential target for liver cancer therapy, the Chakraborty Lab is devising strategies that interfere with the protein coding gene AGRN (Agrin) signaling and impair the mechanotransduction pathway to restrain tumor growth and spread.

Our pioneering work has established that Agrin is frequently overexpressed and secreted in liver cancers. Here we combine advanced biochemical, mechanobiological, three-dimensional approaches and genetic and syngeneic in vivo mouse models to elucidate how Agrin orchestrates its oncogenic potential in cancer cells and their surrounding microenvironment.

For instance, we study how Agrin from cancer cells recruit endothelial cells and/or other immune cells to the tumor microenvironment that may fuel carcinogenesis. A detailed mechanistic understanding of the Agrin-mechanotransductive signaling network is essential for devising new targeting strategies.

Cell slide from a microscope
A mechanically stretched cancer cell (red-F-Actin) responding to high Agrin and promoting nuclear (blue) YAP assembly (green).

Further studies showed that Agrin shapes up the mechanical landscape of the tumor microenvironment (TME) and modulates angiogenesis by stabilizing VEGFR2 in the endothelial cells:

Our latest evidence shows a promising role of sAgrin therapy to activate YAP/TAZ during diabetic skin wound healing:

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Department of Pharmacology & Therapeutics
Roswell Park Comprehensive Cancer Center
Elm and Carlton Streets
Buffalo, NY 14263