Transmembrane 4 L six family member 1 (TM4SF1)

Transmembrane 4 L six family member 1 (TM4SF1) is a cell surface protein encoded by the TM4SF1 gene, structurally characterized by four hydrophobic transmembrane domains similar to tetraspanins but classified into the L6 family. TM4SF1 is predominantly localized to the plasma membrane and organelles such as lysosomes, and functions as a regulator of cell motility, adhesion, proliferation, and angiogenesis. It is highly expressed in various carcinoma cells and the vascular endothelium of tumors, but shows limited expression in most normal adult tissues. TM4SF1 mediates signal transduction crucial for cancer cell migration, invasion (often via epithelial-mesenchymal transition), angiogenesis, and metastatic reactivation through interactions with integrins (notably α6β1, α6β4), receptor tyrosine kinases (e.g., DDR1), and formation of tetraspanin-enriched microdomains. It is implicated as a prognostic biomarker in cancers and a potential therapeutic target, especially for antibody-based strategies aiming to inhibit pathological angiogenesis and tumor progression. TM4SF1 is also reported as a marker for epithelial progenitor cells and is upregulated in regenerative and inflammatory lung states. No FDA-approved direct TM4SF1-targeted drugs are currently available, but preclinical development is ongoing.

Other names

L6 antigenL6M3S1Gene symbol: TM4SF1

Antibody-dependent cellular cytotoxicity (ADCC); Complement-dependent cytotoxicity (CDC); Inhibition of tumor cell migration, proliferation, and angiogenesis by blocking TM4SF1 function/expression