Afadin cooperates with Claudin-2 to promote breast cancer metastasis

Research output: Contribution to journalArticle


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.}",
year = "2019",
doi = "10.1101/gad.319194.118",
language = "English",
volume = "33",
pages = "180--193",
journal = "Genes and Development",
issn = "1549-5477",
publisher = "Cold Spring Harbor Laboratory Press",
number = "3-4",