GIPC in Cancer Therapeutics

The Tumor Angiogenesis and Vascular Biology Laboratory studies peptides and small molecules that inhibit GAIP-interacting protein C terminus (GIPC).

GIPC has been implicated in a number of physiological and pathological processes, including cancer. GIPC contains a PDZ domain that can bind to various PDZ domain-binding proteins, including endoglin, glucose trasporter-1 (Glut-1), insulin-like growth factor-I receptor (IGF-1R), integrins and neuropilin-1 (NRP1). It's also a critical player in the biology of normal and malignant cells.

The binding mode of GIPC PDZ involves direct association with the C-terminal tail of its endogenous partner proteins. These protein-protein interactions could be disrupted by GIPC PDZ specific inhibitors.

Dr. Mukhopadhyay's lab designed several cell-permeable, linear lipopeptide inhibitors, successfully used these inhibitors to disrupt the binding of partner proteins — such as IGF-1R and endoglin — to GIPC PDZ, and showed their efficacy in inhibiting the proliferation of pancreatic and breast cancer cells in vitro and tumor growth in vivo.

Dr. Mukhopadhyay's Tumor Angiogenesis and Vascular Biology Lab is now developing more-potent inhibitory peptides and small molecules to target GIPC and its partner proteins. The inhibitors will be employed to analyze GIPC's central role in different classes of cancer growth and metastasis, which will help scientists predict and design new personalized therapies for patients.