CHC promotes tumor growth and angiogenesis through regulation of HIF-1α and VEGF signaling

Pancreatic adenocarcinoma is an aggressive disease with a high mortality rate. In this study, we have newly generated a monoclonal antibody (mAb), Pa65-2, which specifically binds to pancreatic cancer cells and tumor blood vessels. The target protein of Pa65-2 is identified as human clathrin heavy chain (CHC). In vitro and In vivo study showed that suppression of CHC either by shRNA or by Pa65-2 inhibited tumor growth and angiogenesis. One of the key functions of CHC was to bind with the hypoxia-inducing factor (HIF)-1α protein, increasing the stability of this protein and facilitating its nuclear translocation, thereby regulating the expression of VEGF. Taken together, our findings indicate that CHC plays a role in the processes of tumorigenesis and angiogenesis. Pa65-2 antibody or CHC shRNA can potentially be used for pancreatic cancer therapy.

► CHC promotes tumor growth, invasion and angiogenesis in vitro and in vivo. ► CHC interacts with and stabilizes HIF-1α, and leads to an increased production of VEGF. ► Pa65-2 antibody can potentially be used to inhibit tumor angiogenesis and growth.