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Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties

Oncogene volume 31, pages 3709–3720 (2012)Cite this article

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Abstract

Alpha B-crystallin (CRYAB) maps within the nasopharyngeal carcinoma (NPC) tumor-suppressive critical region 11q22-23 and its downregulation is significantly associated with the progression of NPC. However, little is known about the functional impact of CRYAB on NPC progression. In this study we evaluated the NPC tumor-suppressive and progression-associated functions of CRYAB. Activation of CRYAB suppressed NPC tumor formation in nude mice. Overexpression of CRYAB affected NPC progression-associated phenotypes such as loss of cell adhesion, invasion, interaction with the tumor microenvironment, invasive protrusion formation in three dimensional Matrigel culture, as well as expression of epithelial–mesenchymal transition-associated markers. CRYAB mediates this ability to suppress cancer progression by inhibition of E-cadherin cytoplasmic internalization and maintenance of β-catenin in the membrane that subsequently reduces the levels of expression of critical downstream targets such as cyclin-D1 and c-myc. Both ectopically expressed and recombinant CRYAB proteins were associated with endogenous E-cadherin and β-catenin, and, thus, the cadherin/catenin adherens junction. The CRYAB α-crystallin core domain is responsible for the interaction of CRYAB with both E-cadherin and β-catenin. Taken together, these results indicate that CRYAB functions to suppress NPC progression by associating with the cadherin/catenin adherens junction and modulating the β-catenin function.

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Acknowledgements

We thank Patrick Vicart for the pcDNA3-CRYAB construct. We acknowledge the funding support from the Research Grants Council grants, and the University Grants Council of Hong Kong Special Administrative Region, People's Republic of China, for AoE/M-06/08 to MLL; The University of Hong Kong Seed Funding Programme for Basic Research to HLL; and the Swedish Cancer Society, the Swedish Research Council, the Swedish Institute and Karolinska Institute to ERZ. We acknowledge the Area of Excellence Hong Kong NPC Research Tissue Bank for the NPC specimens and tissue blocks.

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Authors and Affiliations

  1. Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Hong Kong (SAR), PR China

    Z Huang, Y Cheng, P M Chiu, D L-W Kwong, H L Lung & M L Lung

  2. Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Hong Kong (SAR), PR China

    F M F Cheung

  3. Department of Pathology, University of Hong Kong, Hong Kong (SAR), PR China

    J M Nicholls

  4. Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong (SAR), PR China

    A W M Lee

  5. Department of Microbiology, Department of Clinical Science and Education, Tumor and Cell Biology, Sodersjukhuset, Karolinska Institute, Stockholm, Sweden

    E R Zabarovsky

  6. Laboratory of Structural and Functional Genomics, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

    E R Zabarovsky

  7. Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA

    E J Stanbridge

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  1. Z Huang
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Huang, Z., Cheng, Y., Chiu, P. et al. Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties. Oncogene 31, 3709–3720 (2012). https://doi.org/10.1038/onc.2011.529

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