title: Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties.
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.
authors.affiliation: Department of Clinical Oncology and Center for Cancer Research, University of Hong Kong, Hong Kong (SAR), PR China.
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Cheng
authors.forename: P M
authors.initials: PM
authors.lastname: Chiu
authors.forename: F M F
authors.initials: FM
authors.lastname: Cheung
authors.forename: J M
authors.initials: JM
authors.lastname: Nicholls
authors.forename: D L-W
authors.initials: DL
authors.lastname: Kwong
authors.forename: A W M
authors.initials: AW
authors.lastname: Lee
authors.forename: E R
authors.initials: ER
authors.lastname: Zabarovsky
authors.forename: E J
authors.initials: EJ
authors.lastname: Stanbridge
authors.forename: H L
authors.initials: HL
authors.lastname: Lung
authors.forename: M L
authors.initials: ML
authors.lastname: Lung
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D021381:Protein Transport; D047368:Tumor Burden; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D038203:alpha-Crystallin B Chain / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C059215:CRYAB protein, human; D015820:Cadherins; D025521:Tumor Suppressor Proteins; D038203:alpha-Crystallin B Chain; D051176:beta Catenin