Wnt1-inducible signaling pathway protein 1 (WISP-1) (WISP-1)

Wnt1-inducible signaling pathway protein 1 (WISP-1), also known as CCN4, is a secreted matricellular protein belonging to the CCN family [1, 5]. It was originally identified as a downstream target of the Wnt1 signaling pathway and functions as a bridge between the extracellular matrix and cell surface receptors [1, 8]. WISP-1 regulates essential cellular processes including proliferation, migration, and survival by activating signaling cascades such as the PI3K/Akt and mTOR pathways [1, 4, 15]. In healthy tissues, it is involved in bone homeostasis, wound healing, and providing cytoprotection against oxidative stress [6, 9, 11]. Pathologically, WISP-1 is a significant driver of fibrosis in the lungs, liver, and heart, where it promotes myofibroblast activation and collagen deposition [8, 10, 12]. It also plays a prominent role in oncology, where its overexpression is associated with tumor progression, epithelial-mesenchymal transition, and poor prognosis in various cancers [5, 13, 14]. Therapeutic efforts are currently exploring the use of monoclonal antibodies, such as MTX-463, to neutralize WISP-1 activity in patients with idiopathic pulmonary fibrosis [10]. Given its pleiotropic effects, targeting WISP-1 offers a promising approach for treating both fibro-proliferative diseases and certain aggressive malignancies [1, 5].

Other names

CCN4WISP1Wnt-induced secreted protein-1ELM1Wnt1-inducible signaling pathway protein 1

Monoclonal antibody-mediated neutralization of WISP-1 to inhibit downstream pro-fibrotic and pro-oncogenic signaling pathways such as PI3K/Akt and mTOR [10, 17].