AGO2 role in pancreatic cancer development


MCTP researchers, led by Dr. Sunita Shankar, have identified a protein — Argonaute 2 — that appears to be critical for the progression of benign precursor lesions into pancreatic cancer. Both KRAS and EGFR are essential mediators of pancreatic cancer development and interact with Argonaute 2 (AGO2) to perturb its function. Here, using a mouse model of mutant KRAS-driven pancreatic cancer, they showed that loss of AGO2 allowed precursor lesion (PanIN) formation yet prevented progression to pancreatic ductal adenocarcinoma (PDAC). In mouse and human pancreatic tissues, PDAC progression was associated with increased plasma membrane localization of RAS/AGO2. Altogether, this study supports a biphasic model of pancreatic cancer development: an AGO2-independent early phase of PanIN formation reliant on EGFR-RAS signaling, and an AGO2-dependent phase wherein the mutant KRAS-AGO2 interaction is critical for PDAC progression. These finding were published in Nature Communications.

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