Afadin cooperates with Claudin-2 to promote breast cancer metastasis

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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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; Simon, Hans Georg; Walsh, Logan A.; Kimbung, Siker; Hedenfalk, Ingrid; Siegel, Peter M.

I: Genes & Development, Vol. 33, Nr. 3-4, 2019, s. 180-193.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Tabariès, S, McNulty, A, Ouellet, V, Annis, MG, Dessureault, M, Vinette, M, Hachem, Y, Lavoie, B, Omeroglu, A, Simon, HG, Walsh, LA, Kimbung, S, Hedenfalk, I & Siegel, PM 2019, 'Afadin cooperates with Claudin-2 to promote breast cancer metastasis', Genes & Development, vol. 33, nr. 3-4, s. 180-193. https://doi.org/10.1101/gad.319194.118

APA

Tabariès, S., McNulty, A., Ouellet, V., Annis, M. G., Dessureault, M., Vinette, M., ... Siegel, P. M. (2019). Afadin cooperates with Claudin-2 to promote breast cancer metastasis. Genes & Development, 33(3-4), 180-193. https://doi.org/10.1101/gad.319194.118

CBE

Tabariès S, McNulty A, Ouellet V, Annis MG, Dessureault M, Vinette M, Hachem Y, Lavoie B, Omeroglu A, Simon HG, Walsh LA, Kimbung S, Hedenfalk I, Siegel PM. 2019. Afadin cooperates with Claudin-2 to promote breast cancer metastasis. Genes & Development. 33(3-4):180-193. https://doi.org/10.1101/gad.319194.118

MLA

Vancouver

Tabariès S, McNulty A, Ouellet V, Annis MG, Dessureault M, Vinette M et al. Afadin cooperates with Claudin-2 to promote breast cancer metastasis. Genes & Development. 2019;33(3-4):180-193. https://doi.org/10.1101/gad.319194.118

Author

Tabariès, Sébastien ; McNulty, Alexander ; Ouellet, Véronique ; Annis, Matthew G. ; Dessureault, Mireille ; Vinette, Maude ; Hachem, Yasmina ; Lavoie, Brennan ; Omeroglu, Atilla ; Simon, Hans Georg ; Walsh, Logan A. ; Kimbung, Siker ; Hedenfalk, Ingrid ; Siegel, Peter M. / Afadin cooperates with Claudin-2 to promote breast cancer metastasis. I: Genes & Development. 2019 ; Vol. 33, Nr. 3-4. s. 180-193.

RIS

TY - JOUR

T1 - Afadin cooperates with Claudin-2 to promote breast cancer metastasis

AU - Tabariès, Sébastien

AU - McNulty, Alexander

AU - Ouellet, Véronique

AU - Annis, Matthew G.

AU - Dessureault, Mireille

AU - Vinette, Maude

AU - Hachem, Yasmina

AU - Lavoie, Brennan

AU - Omeroglu, Atilla

AU - Simon, Hans Georg

AU - Walsh, Logan A.

AU - Kimbung, Siker

AU - Hedenfalk, Ingrid

AU - Siegel, Peter M.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - Afadin

KW - breast cancer

KW - Claudin-2

KW - liver metastasis

KW - lung metastasis

U2 - 10.1101/gad.319194.118

DO - 10.1101/gad.319194.118

M3 - Article

VL - 33

SP - 180

EP - 193

JO - Genes and Development

T2 - Genes and Development

JF - Genes and Development

SN - 1549-5477

IS - 3-4

ER -