Transmembrane 4 L6 family member 1 (TM4SF1) (TM4SF1)

Transmembrane 4 L6 family member 1 (TM4SF1) is a small plasma membrane glycoprotein belonging to the L6 superfamily, characterized by four transmembrane domains and two extracellular loops [1]. It is highly overexpressed in a wide variety of solid tumors, including lung, breast, pancreatic, and colorectal cancers, and is also notably present on tumor-associated vascular endothelial cells [4]. TM4SF1 functions as a molecular scaffold that promotes cell migration, proliferation, and angiogenesis by regulating the recruitment of signaling proteins like syntenin-1 and DDR1 to the cell surface [3]. In clinical oncology, TM4SF1 is recognized as a driver of metastasis and the epithelial-mesenchymal transition (EMT) [4]. Because of its high tumor-to-normal tissue expression ratio and its dual role in targeting both tumor cells and the supporting vasculature, it has become a high-priority target for antibody-drug conjugates (ADCs) [2]. Therapeutic candidates such as vobasertamab mafodotin (PF-06647020) have been developed to exploit this target, delivering cytotoxic payloads directly to malignant cells and the tumor microenvironment [2]. [1] UniProt Consortium, P30408; [2] Bullock et al. (2018) PMID: 29330210; [3] Zukauskas et al. (2011) PMID: 21681446; [4] Gao et al. (2019) PMID: 30704501.

Other names

L6 antigenMembrane component chromosome 3 surface marker 1M3S1Tumor-associated antigen L6TAAL6Transmembrane 4 superfamily member 1

Antibody-drug conjugate (ADC) mediated delivery of cytotoxic agents; Radioimmunotherapy targeting tumor cells and tumor-associated vasculature