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

• Published in: Oncogene Vol. 31; no. 32; pp. 3709 - 3720
• Main Authors: Huang, Z, Cheng, Y, Chiu, P M, Cheung, F M F, Nicholls, J M, Kwong, D L-W, Lee, A W M, Zabarovsky, E R, Stanbridge, E J, Lung, H L, Lung, M L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.08.2012; Nature Publishing Group
• Subjects: 631/67/581; 631/80/79/2028; 692/699/67/1536; adherens junctions; Adherens Junctions - metabolism; alpha -Crystallin; alpha-Crystallin B Chain - metabolism; Animals; Apoptosis; beta Catenin - metabolism; c-Myc protein; Cadherin; Cadherins - metabolism; Carcinoma - metabolism; Carcinoma - pathology; catenin; Cell Adhesion; Cell adhesion & migration; Cell Biology; Cell culture; Cell Line, Tumor; Cell Movement; Crystallin; Disease Progression; E-Cadherin; Female; Gene expression; Genetic code; Head & neck cancer; Human Genetics; Humans; Internal Medicine; Internalization; Invasiveness; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Mesenchyme; Mice; Mice, Inbred BALB C; Mice, Nude; Microenvironments; Myc protein; Nasopharyngeal cancer; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; Neoplasm Invasiveness; Neoplasm Transplantation; Oncology; original-article; Phenotypes; Protein Transport; Proteins; Throat cancer; Tumor Burden; Tumor microenvironment; Tumor suppressor genes; Tumor Suppressor Proteins - metabolism; Tumors; β-Catenin; United States; β-catenin; E-cadherin; nasopharyngeal carcinoma
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/onc.2011.529

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.