CCN4

CCN4 encodes a matricellular protein in the connective tissue growth factor family that is induced by WNT1 and functions as a downstream effector of Wnt/Frizzled signaling. It is highly expressed in colon tumors and in multiple adult tissues, with strong expression reported in connective tissue and high protein expression in the brain, proximal digestive tract, and gastrointestinal tract. The protein is found in the extracellular region as well as the cytosol and cytoplasm. CCN4 promotes cell survival by activating AKT kinase, which suppresses p53-mediated apoptosis and up-regulates the anti-apoptotic protein Bcl-X(L). It binds the extracellular matrix proteoglycans decorin and biglycan, two small leucine-rich proteoglycans, and this binding has been linked to inhibition of their effects on tumor cell proliferation. These features place CCN4 at the interface of secreted signaling, extracellular matrix regulation, and survival signaling.