Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties
Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties
复制标题
DOI：
10.1038/onc.2011.529
复制
发表时间：
2012-08-01
期刊：
影响因子：
8
通讯作者：
Lung, M. L.
中科院分区：
文献类型：
--
作者：
Huang, Z.;Cheng, Y.;Lung, M. L.
α b -晶体蛋白（CRYAB）位于鼻咽癌（NPC）肿瘤抑制关键区11q22-23内，其下调与鼻咽癌的进展显著相关。然而，关于CRYAB对NPC进展的功能影响知之甚少。在这项研究中，我们评估了CRYAB的鼻咽癌肿瘤抑制和进展相关功能。激活CRYAB抑制裸鼠鼻咽癌肿瘤形成。CRYAB的过表达影响鼻咽癌进展相关表型，如细胞粘附丧失、侵袭、与肿瘤微环境的相互作用、三维基质培养中侵袭性突起的形成，以及上皮-间充质过渡相关标志物的表达。CRYAB通过抑制E-cadherin细胞质内化和维持膜中β -catenin，从而降低关键下游靶点（如cyclin-D1和c-myc）的表达水平，介导这种抑制癌症进展的能力。异位表达和重组CRYAB蛋白都与内源性E-cadherin和β -catenin有关，因此，与cadherin/catenin粘附连接有关。CRYAB α -结晶蛋白核心结构域负责CRYAB与E-cadherin和β -catenin的相互作用。综上所述，这些结果表明CRYAB通过与cadherin/catenin粘附体连接并调节β -catenin功能来抑制NPC进展。中华肿瘤杂志，2012,31 (3):397 - 397；doi: 10.1038 / onc.2011.529;2011年12月12日在线发布
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 beta-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 beta-catenin, and, thus, the cadherin/catenin adherens junction. The CRYAB alpha-crystallin core domain is responsible for the interaction of CRYAB with both E-cadherin and beta-catenin. Taken together, these results indicate that CRYAB functions to suppress NPC progression by associating with the cadherin/catenin adherens junction and modulating the beta-catenin function. Oncogene (2012) 31, 3709-3720; doi:10.1038/onc.2011.529; published online 12 December 2011