@article{b58042807fde454195667d341b17e508,
title = "Afadin cooperates with claudin-2 to promote breast cancer metastasis",
abstract = "Claudin-2 promotes breast cancer liver metastasis by enabling seeding and early cancer cell survival. We now demonstrate that the PDZ-binding motif of Claudin-2 is necessary for anchorage-independent growth of cancer cells and is required for liver metastasis. Several PDZ domain-containing proteins were identified that interact with the PDZ-binding motif of Claudin-2 in liver metastatic breast cancer cells, including Afadin, Arhgap21, Pdlim2, Pdlim7, Rims2, Scrib, and ZO-1. We specifically examined the role of Afadin as a potential Claudin-2-interacting partner that promotes breast cancer liver metastasis. Afadin associates with Claudin-2, an interaction that requires the PDZ-binding motif of Claudin-2. Loss of Afadin also impairs the ability of breast cancer cells to form colonies in soft agar and metastasize to the lungs or liver. Immunohistochemical analysis of Claudin-2 and/or Afadin expression in 206 metastatic breast cancer tumors revealed that high levels of both Claudin-2 and Afadin in primary tumors were associated with poor disease-specific survival, relapse-free survival, lung-specific relapse, and liver-specific relapse. Our findings indicate that signaling downstream from a Claudin-2/Afadin complex enables the efficient formation of breast cancer metastases. Moreover, combining Claudin-2 and Afadin as prognostic markers better predicts the potential of breast cancer to metastasize to soft tissues.",
keywords = "Afadin, Breast cancer, Claudin-2, Liver metastasis, Lung metastasis",
author = "S{\'e}bastien Tabari{\`e}s and Alexander McNulty and V{\'e}ronique Ouellet and Annis, {Matthew G.} and Mireille Dessureault and Maude Vinette and Yasmina Hachem and Brennan Lavoie and Atilla Omeroglu and Simon, {Hans Georg} and Walsh, {Logan A.} and Siker Kimbung and Ingrid Hedenfalk and Siegel, {Peter M.}",
note = "Funding Information: We acknowledge the Goodman Cancer Research Centre (GCRC) Histology Core Facility (McGill University) for routine histolog-ical services. We acknowledge the GCRC Genetic Perturbation Services (McGill University) for providing us with shRNAs, and the Proteomics Core Facility from the Institute for Research in Immunology and Cancer (Universit{\'e} de Montr{\'e}al) for performing the mass spectrometry experiments and subsequent analysis. We thank members of the Siegel laboratory for thoughtful discussions and critical reading of the manuscript. This work was supported by an operating grant to P.M.S. from the Canadian Institutes of Health Research (CIHR MOP-136907). A.M., M.D., and M.V. acknowledge support from the McGill Integrated Cancer Research Training Program. P.M.S. is a McGill University William Dawson Scholar. Funding Information: We acknowledge the Goodman Cancer Research Centre (GCRC) Histology Core Facility (McGill University) for routine histological services. We acknowledge the GCRC Genetic Perturbation Services (McGill University) for providing us with shRNAs, and the Proteomics Core Facility from the Institute for Research in Immunology and Cancer (Universit{\'e} de Montr{\'e}al) for performing the mass spectrometry experiments and subsequent analysis. We thank members of the Siegel laboratory for thoughtful discussions and critical reading of the manuscript. This work was supported by an operating grant to P.M.S. from the Canadian Institutes of Health Research (CIHR MOP-136907). A.M., M.D., and M.V. acknowledge support from the McGill Integrated Cancer Research Training Program. P.M.S. is a McGill University William Dawson Scholar. Publisher Copyright: {\textcopyright} 2019 Tabari{\`e}s et al.",
year = "2019",
month = feb,
doi = "10.1101/gad.319194.118",
language = "English (US)",
volume = "33",
pages = "180--193",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "3-4",
}
