Zinc transporter ZIP6 (LIV-1) (LIV-1)

Zinc transporter ZIP6, widely known as LIV-1 (SLC39A6), is a multi-pass transmembrane protein that functions as a member of the ZIP family of zinc transporters [PubMed: 12837761]. Originally identified as an estrogen-inducible gene in breast cancer, it is now recognized as a key driver of the epithelial-to-mesenchymal transition (EMT) by regulating the nuclear localization of the Snail transcription factor [PubMed: 22431520]. The protein's name 'LIV-1' is derived from its sequence homology to the bacterial leucine-isoleucine-valine binding protein, although its primary biochemical role in humans involves the transport of zinc ions rather than amino acids [PubMed: 12837761]. Because LIV-1 is highly expressed on the surface of several solid tumors—particularly breast, prostate, and pancreatic cancers—while having limited expression in normal tissues, it has become a prominent target for oncology therapeutics. The most advanced therapeutic approach is the development of antibody-drug conjugates (ADCs) such as ladiratuzumab vedotin, which utilize anti-LIV-1 antibodies to deliver potent cytotoxic payloads directly to malignant cells [PubMed: 27124445]. Targeting LIV-1 aims to inhibit metastatic progression and tumor growth in patients with high expression of the protein.

Other names

SLC39A6ZIP6Zinc transporter 6Estrogen-regulated protein LIV-1Leucine-isoleucine-valine binding protein-like zinc transporterLIV1

The primary clinical mechanism involves the use of antibody-drug conjugates (ADCs) that target the extracellular domain of LIV-1 to deliver a cytotoxic payload, such as monomethyl auristatin E (MMAE), which disrupts microtubules and induces apoptosis in cancer cells [PubMed: 27124445].