A network map of cytoskeleton-associated protein 4 (CKAP4) mediated signaling pathway in cancer

Abstract

Cytoskeleton-associated protein 4 (CKAP4) is a non-glycosylated type II transmembrane protein that serves as a cell surface-activated receptor. It is expressed primarily in the plasma membranes of bladder epithelial cells, type II alveolar pneumocytes, and vascular smooth muscle cells. CKAP4 is involved in various biological activities including cell proliferation, cell migration, keratinocyte differentiation, glycogenesis, fibrosis, thymic development, cardiogenesis, neuronal apoptosis, and cancer. CKAP4 has been described as a pro-tumor molecule that regulates the progression of various cancers, including lung cancer, breast cancer, esophageal squamous cell carcinoma, hepatocellular carcinoma, cervical cancer, oral cancer, bladder cancer, cholangiocarcinoma, pancreatic cancer, myeloma, renal cell carcinoma, melanoma, squamous cell carcinoma, colorectal cancer, and osteosarcoma. CKAP4 and its isoform bind to DKK1 or DKK3 (Dickkopf proteins) or antiproliferative factor (APF) and regulates several downstream signaling cascades. The CKAP4 complex plays a crucial role in regulating the signaling pathways including PI3K/AKT and MAPK1/3. Recently, CKAP4 has been recognized as a potential target for cancer therapy. Due to its biomedical importance, we integrated a network map of CKAP4. The available literature on CKAP4 signaling was manually curated according to the NetPath annotation criteria. The consolidated pathway map comprises 41 activation/inhibition events, 21 catalysis events, 35 molecular associations, 134 gene regulation events, 83 types of protein expression, and six protein translocation events. CKAP4 signaling pathway map data is freely accessible through the WikiPathways Database (https://www.wikipathways.org/index.php/Pathway:WP5322).