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Afadin cooperates with Claudin-2 to promote breast cancer metastasis

Tabariès, Sébastien; McNulty, Alexander; Ouellet, Véronique; Annis, Matthew G.; Dessureault, Mireille; Vinette, Maude; Hachem, Yasmina; Lavoie, Brennan; Omeroglu, Atilla and Simon, Hans Georg, et al. (2019) In Genes & Development 33(3-4). p.180-193
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... (More)

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.

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Contribution to journal
publication status
published
subject
keywords
Afadin, breast cancer, Claudin-2, liver metastasis, lung metastasis
in
Genes & Development
volume
33
issue
3-4
pages
14 pages
publisher
Cold Spring Harbor Laboratory Press
external identifiers
  • scopus:85060927487
ISSN
1549-5477
DOI
10.1101/gad.319194.118
language
English
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yes
id
5079aa00-4818-4326-a23e-b6cd6835b4b3
date added to LUP
2019-02-11 13:54:28
date last changed
2019-02-11 14:49:21
@article{5079aa00-4818-4326-a23e-b6cd6835b4b3,
  abstract     = {<p>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.</p>},
  author       = {Tabariès, Sébastien and McNulty, Alexander and Ouellet, Véronique and Annis, Matthew G. and Dessureault, Mireille and Vinette, Maude and Hachem, Yasmina and Lavoie, Brennan and Omeroglu, Atilla and Simon, Hans Georg and Walsh, Logan A. and Kimbung, Siker and Hedenfalk, Ingrid and Siegel, Peter M.},
  issn         = {1549-5477},
  keyword      = {Afadin,breast cancer,Claudin-2,liver metastasis,lung metastasis},
  language     = {eng},
  number       = {3-4},
  pages        = {180--193},
  publisher    = {Cold Spring Harbor Laboratory Press},
  series       = {Genes & Development},
  title        = {Afadin cooperates with Claudin-2 to promote breast cancer metastasis},
  url          = {http://dx.doi.org/10.1101/gad.319194.118},
  volume       = {33},
  year         = {2019},
}