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A20 promotes metastasis of aggressive basal-like breast cancers through multi-monoubiquitylation of Snail1

(2017) NATURE CELL BIOLOGY. 19(10). p.1260-1273
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Abstract
Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-beta 1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1. Monoubiquitylated Snail1 has reduced affinity for glycogen synthase kinase 3 beta (GSK3 beta), and is thus stabilized in the nucleus through decreased phosphorylation. Knockdown of A20 or overexpression of Snail1 with mutation of the monoubiquitylated lysine residues into arginine abolishes lung metastasis in mouse xenograft and orthotopic breast cancer models, indicating that A20 and monoubiquitylated Snail1 are required for metastasis. Our findings uncover an essential role of the A20-Snail1 axis in TGF-beta 1-induced EMT and metastasis of basal-like breast cancers.
Keywords
NF-KAPPA-B, EPITHELIAL-MESENCHYMAL TRANSITION, NECROSIS-FACTOR-ALPHA, SYSTEMIC-LUPUS-ERYTHEMATOSUS, ZINC-FINGER PROTEIN, TRANSCRIPTION FACTOR, GENE-EXPRESSION, CELL-MIGRATION, TUMOR-CELLS, TGF-BETA

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Chicago
Lee, Ji-Hyung, Su Myung Jung, Kyung-Min Yang, Eunjin Bae, Sung Gwe Ahn, Jin Seok Park, Dongyeob Seo, et al. 2017. “A20 Promotes Metastasis of Aggressive Basal-like Breast Cancers Through Multi-monoubiquitylation of Snail1.” Nature Cell Biology 19 (10): 1260–1273.
APA
Lee, J.-H., Jung, S. M., Yang, K.-M., Bae, E., Ahn, S. G., Park, J. S., Seo, D., et al. (2017). A20 promotes metastasis of aggressive basal-like breast cancers through multi-monoubiquitylation of Snail1. NATURE CELL BIOLOGY, 19(10), 1260–1273.
Vancouver
1.
Lee J-H, Jung SM, Yang K-M, Bae E, Ahn SG, Park JS, et al. A20 promotes metastasis of aggressive basal-like breast cancers through multi-monoubiquitylation of Snail1. NATURE CELL BIOLOGY. 2017;19(10):1260–73.
MLA
Lee, Ji-Hyung et al. “A20 Promotes Metastasis of Aggressive Basal-like Breast Cancers Through Multi-monoubiquitylation of Snail1.” NATURE CELL BIOLOGY 19.10 (2017): 1260–1273. Print.
@article{8537854,
  abstract     = {Although the ubiquitin-editing enzyme A20 is a key player in inflammation and autoimmunity, its role in cancer metastasis remains unknown. Here we show that A20 monoubiquitylates Snail1 at three lysine residues and thereby promotes metastasis of aggressive basal-like breast cancers. A20 is significantly upregulated in human basal-like breast cancers and its expression level is inversely correlated with metastasis-free patient survival. A20 facilitates TGF-beta 1-induced epithelial-mesenchymal transition (EMT) of breast cancer cells through multi-monoubiquitylation of Snail1. Monoubiquitylated Snail1 has reduced affinity for glycogen synthase kinase 3 beta (GSK3 beta), and is thus stabilized in the nucleus through decreased phosphorylation. Knockdown of A20 or overexpression of Snail1 with mutation of the monoubiquitylated lysine residues into arginine abolishes lung metastasis in mouse xenograft and orthotopic breast cancer models, indicating that A20 and monoubiquitylated Snail1 are required for metastasis. Our findings uncover an essential role of the A20-Snail1 axis in TGF-beta 1-induced EMT and metastasis of basal-like breast cancers.},
  author       = {Lee, Ji-Hyung and Jung, Su Myung and Yang, Kyung-Min and Bae, Eunjin and Ahn, Sung Gwe and Park, Jin Seok and Seo, Dongyeob and Kim, Minbeom and Ha, Jihoon and Lee, Jaewon and Kim, Jun-Hyeong and Kim, Jun Hwan and Ooshima, Akira and Park, Jinah and Shin, Donghyuk and Lee, Youn Sook and Lee, Sangho and van Loo, Geert and Jeong, Joon and Kim, Seong-Jin and Park, Seok Hee},
  issn         = {1465-7392},
  journal      = {NATURE CELL BIOLOGY},
  keywords     = {NF-KAPPA-B,EPITHELIAL-MESENCHYMAL TRANSITION,NECROSIS-FACTOR-ALPHA,SYSTEMIC-LUPUS-ERYTHEMATOSUS,ZINC-FINGER PROTEIN,TRANSCRIPTION FACTOR,GENE-EXPRESSION,CELL-MIGRATION,TUMOR-CELLS,TGF-BETA},
  language     = {eng},
  number       = {10},
  pages        = {1260--1273},
  title        = {A20 promotes metastasis of aggressive basal-like breast cancers through multi-monoubiquitylation of Snail1},
  url          = {http://dx.doi.org/10.1038/ncb3609},
  volume       = {19},
  year         = {2017},
}

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