Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties
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 ev...
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Published in | Oncogene Vol. 31; no. 32; pp. 3709 - 3720 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
09.08.2012
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 0950-9232 1476-5594 1476-5594 |
DOI: | 10.1038/onc.2011.529 |