WNT1-inducible-signaling pathway protein 1 (WISP1) (WISP1)

WNT1-inducible-signaling pathway protein 1 (WISP1), also known as CCN4, is a secreted matricellular protein belonging to the CCN family that plays a critical role in mediating cell-to-cell and cell-to-matrix communications. It is typically induced by the canonical Wnt/beta-catenin signaling pathway and serves as a key regulator of the extracellular matrix (ECM) environment, influencing cell proliferation, survival, and migration across various tissues. In healthy physiology, WISP1 is involved in embryonic development, bone turnover, and tissue repair; however, its pathological overexpression is strongly associated with the progression of fibrosis and cancer. In oncology, WISP1 acts as a pro-tumorigenic factor by promoting epithelial-mesenchymal transition (EMT), angiogenesis, and resistance to apoptosis in several malignancies, including gastric, breast, and lung cancers. In fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and liver cirrhosis, WISP1 facilitates myofibroblast activation and excessive collagen deposition. Current therapeutic development focuses on neutralizing WISP1 with monoclonal antibodies to block its interaction with cell surface receptors, such as integrins and low-density lipoprotein receptor-related proteins (LRPs), thereby halting disease progression. Clinical candidates like MTX-463 are currently undergoing evaluation in trials for their potential to treat severe fibrotic conditions.

Other names

CCN4Cellular communication network factor 4WISP-1WISP1cWISP1iWISP1tcWNT1-inducible-signaling pathway protein 1

Neutralization of WISP1 protein to inhibit binding to integrins (e.g., alpha-v beta-3) and LRP receptors, thereby blocking downstream pro-fibrotic and pro-oncogenic signaling pathways.