Switch-associated protein 70 (SWAP-70)

Switch-associated protein 70 (SWAP-70) is a multifunctional protein that acts as a phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent guanine nucleotide exchange factor (GEF) and a unique F-actin bundling protein (UniProt Q9UH65; PubMed 10681448, 23921380). It is primarily expressed in hematopoietic cells, where it plays a pivotal role in B-cell isotype switching, dendritic cell migration, and mast cell activation (PubMed 11929948, 21307294). SWAP-70 facilitates the reorganization of the actin cytoskeleton by tethering F-actin to the plasma membrane and stabilizing activated Rac1, which is essential for processes like lamellipodia formation, phagocytosis, and cell motility (PubMed 28489960, 31932501). In the context of disease, SWAP-70 is recognized as a potential oncogene and a promoter of tumor metastasis; its overexpression or mutation enhances the invasive and migratory capabilities of cancer cells in breast, lung, and ovarian cancers (PubMed 23555004, 38755184). Conversely, in the cardiovascular system, SWAP-70 exerts a protective effect against pathological cardiac hypertrophy by inhibiting the TAK1 signaling pathway (PubMed 36974738). While specific clinical drugs targeting SWAP-70 are not yet approved, small molecules like sanguinarine have been identified as putative inhibitors, and its role in metastasis and inflammation makes it a compelling target for future therapeutic development (PubMed 28489960).

Other names

SWAP70KIAA0640HSPC321SWAP switching B-cell complex 70kDa subunitSWAP switching B-cell complex subunit 70

Sanguinarine acts as a putative inhibitor that blocks SWAP-70-mediated F-actin polymerization and phagocytosis. 12(S)-HETE modulates SWAP-70 by inducing its translocation to membrane ruffles where it dimerizes and bundles actin to promote cell motility.