1. Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan
2. Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
3. Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan
4. These authors contributed equally to this work

Correspondence to: Toshio Hirano^1,2,3 Email: hirano@molonc.med.osaka-u.ac.jp
The zebrafish LIV1 cDNA sequence has been deposited in the GenBank database under accession number AB126260.

Abstract

Vertebrate gastrulation is a critical step in the establishment of body plan. During gastrulation, epithelial-mesenchymal transition (EMT) occurs¹. EMT is one of the central events of embryonic development, organ and tissue regeneration, and cancer metastasis^{1, 2}. Signal transducers and activators of transcription (STATs) mediate biological actions such as cell proliferation, differentiation and survival in response to cytokines and growth factors, in a variety of biological processes^{3, 4, 5, 6}. STATs are also important in EMT during gastrulation, organogenesis, wound healing and cancer progression^{7, 8, 9}. We previously showed that STAT3 is activated in the organizer during zebrafish gastrulation and its activity is essential for gastrulation movements. The requirement for STAT3 is cell-autonomous for the anterior migration of gastrula organizer cells, and non-cell-autonomous for the convergence of neighbouring cells¹⁰. The molecular mechanisms of STAT's action in EMT, however, are unknown. Here we identify LIV1, a breast-cancer-associated zinc transporter protein^{11, 12, 13}, as a downstream target of STAT3 that is essential and sufficient for STAT3's cell-autonomous role in the EMT of zebrafish gastrula organizer cells. Furthermore, we demonstrate that LIV1 is essential for the nuclear localization of zinc-finger protein Snail, a master regulator of EMT^{1, 2, 14, 15}. These results establish a molecular link between STAT3, LIV1 and Snail in EMT.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.