Solute carrier family 39 member 6 (LIV-1) (LIV-1)

Solute carrier family 39 member 6 (LIV-1) is a multi-pass transmembrane protein that functions as a zinc transporter, facilitating the influx of zinc into the cytosol (UniProt P55030). It is significantly regulated by estrogen and is a key mediator of the epithelial-mesenchymal transition (EMT), a process essential for tumor metastasis, by regulating the activity of the transcription factor Snail (PubMed: 24631457). LIV-1 is highly expressed in several malignancies, most notably in estrogen receptor-positive breast cancers, as well as prostate, pancreatic, and cervical cancers (PubMed: 29158365). Because its expression is relatively restricted in healthy tissues, it serves as a viable target for antibody-drug conjugates (ADCs) like ladiratuzumab vedotin (SGN-LIV1A). This ADC consists of a humanized anti-LIV-1 antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE). Upon binding to LIV-1 on the cancer cell surface, the complex is internalized via receptor-mediated endocytosis. The subsequent lysosomal release of MMAE leads to tubulin polymerization inhibition, cell cycle arrest, and apoptosis (ClinicalTrials.gov: NCT01969643). Beyond its role as a transporter, LIV-1 is involved in intracellular signaling pathways that promote cell survival and proliferation in the tumor microenvironment. Clinical development of LIV-1 targeted therapies focuses on patients with metastatic triple-negative breast cancer and other LIV-1-expressing solid tumors.

Other names

SLC39A6ZIP6LIV1Estrogen-regulated protein LIV-1Zinc transporter 6

Antibody-drug conjugate binding to the extracellular domain of LIV-1 followed by receptor-mediated endocytosis and lysosomal release of a cytotoxic microtubule inhibitor.