Transmembrane 9 superfamily member 4 (TM9SF4)

Transmembrane 9 superfamily member 4 (TM9SF4) is a multi-pass transmembrane protein that regulates actin cytoskeleton dynamics, specifically acting as an F-actin disassembly factor through a redox mechanism involving oxidation at actin cysteine 374[1][2]. TM9SF4 is directly implicated in the enhancement of cancer cell migration, invasion, and metastasis by promoting cofilin-mediated actin filament disassembly. Knockdown or depletion of TM9SF4 results in impaired cell motility and tumor metastasis in vivo, and its expression levels correlate with aggressive cancer phenotypes[1][2]. Furthermore, TM9SF4 modulates the lineage commitment of bone marrow mesenchymal stem cells, promoting adipogenesis and suppressing osteogenic differentiation through pathways involving Wnt/β-catenin and mTORC2/Akt/β-catenin signaling[3]. The protein is also noted for its role in cell behaviors analogous to phagocytosis and cannibalism, linking it to wider functions in tissue remodeling and potentially immune defense[2][3]. Although TM9SF4 is not yet a therapeutic target with approved drugs, it is under investigation as a potential target, particularly in cancers with high metastatic potential and possibly in osteoporosis[1][2][3].

Other names

KIAA0255TUCAP1dJ836N17.2Tumor cannibalism associated protein 1

For hypothesized therapeutics: Modulation of TM9SF4 expression or function (such as knockdown), which affects redox-dependent actin filament disassembly and inhibits cancer cell migration and metastasis[1][2].