Filamin A-interacting protein 1-like (FILIP1L) (FILIP1L)

Filamin A-interacting protein 1-like (FILIP1L), also known as DOC1, is a tumor suppressor protein that is frequently downregulated in various cancers, including ovarian, prostate, and colon cancers, primarily through promoter hypermethylation [1, 3, 6]. It acts as a potent inhibitor of the canonical Wnt/β-catenin signaling pathway by promoting the degradation of β-catenin at the centrosome, which serves as a proteolytic center [2, 3, 8]. This degradation prevents the nuclear translocation of β-catenin and the subsequent transcriptional activation of oncogenic targets such as matrix metalloproteinases (MMPs) and epithelial-to-mesenchymal transition (EMT) factors like SLUG and SNAIL [2, 3, 8]. The FILIP1LΔC103 variant is a C-terminal truncation mutant (residues 1-790) that exhibits enhanced protein stability and anti-tumor potency compared to the wild-type protein [4, 10, 13]. Experimental therapeutic approaches have utilized gene delivery of FILIP1LΔC103, often in combination with chemotherapy like cisplatin, to inhibit metastasis and angiogenesis in preclinical models [7, 9, 11]. As a therapeutic target, FILIP1L represents a strategy for restoring endogenous growth-inhibitory signaling to suppress cancer progression [1, 11].

Other names

DOC1 [6]Downregulated in Ovarian Cancer 1 [6]GIP130 [6]130 kDa GPBP-interacting protein [6]Filamin A-interacting protein 1-like [6]

Restoration of FILIP1L function inhibits the canonical Wnt/β-catenin signaling pathway by promoting centrosomal degradation of β-catenin, thereby reducing the expression of downstream targets involved in invasion and metastasis [2, 3, 8, 11].