Signal-induced proliferation-associated gene 1 (SIPA1)

Signal-induced proliferation-associated gene 1 (SIPA1) is a GTPase-activating protein (GAP) that specifically targets the Rap1 and Rap2 members of the Ras superfamily. It is predominantly expressed in lymphoid tissues and plays a pivotal role in regulating cell adhesion, motility, and the cell cycle by modulating the activity of Rap GTPases (UniProt P49790; NCBI Gene: 6494). In clinical oncology, SIPA1 is recognized as a significant metastasis-efficiency gene; its overexpression is strongly correlated with increased metastatic potential and poor prognosis in various malignancies, including breast, prostate, and colorectal cancers (PubMed: 12439607, 19633089). Beyond its role in cancer progression, SIPA1 is involved in the regulation of T-cell activation and has been implicated in the progression of chronic myelogenous leukemia (CML). While its central role in metastasis makes it an attractive therapeutic target, there are currently no FDA-approved drugs or clinical-stage small molecules specifically targeting SIPA1. Research remains focused on understanding its scaffolding functions and its interaction with other proteins like Brd4 to drive pro-metastatic gene expression (PubMed: 26109061).

Other names

SPA1SPA-1GTPase-activating protein SPA-1SIPA-1

SIPA1 functions as a GTPase-activating protein (GAP) specific for Rap1 and Rap2, promoting the hydrolysis of GTP to GDP and thereby inactivating these small GTPases to modulate downstream signaling pathways involved in cell adhesion and migration (UniProt P49790; PubMed: 7630730).