CHL1 suppresses tumor growth and metastasis in nasopharyngeal carcinoma by repressing PI3K/AKT signaling pathway via interaction with Integrin β1 and Merlin

Deletion of Chromosome 3p is one of the most frequently detected genetic alterations in nasopharyngeal carcinoma (NPC). We reported the role of a novel 3p26.3 tumor suppressor gene (TSG) in NPC. Down-regulation of was detected in 4/6 of NPC cell lines and 71/95 (74.7%) in clinical tissues. Ectopic e...

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Vydáno v:	International journal of biological sciences Ročník 15; číslo 9; s. 1802 - 1815
Hlavní autoři:	Chen, Juan, Jiang, Chen, Fu, Li, Zhu, Cai-Lei, Xiang, Yan-Qun, Jiang, Ling-Xi, Chen, Qian, Liu, Wai Man, Chen, Jin-Na, Zhang, Li-Yi, Liu, Ming, Chen, Chao, Tang, Hong, Wang, Bo, Tsao, Sai Wah, Kwong, Dora Lai-Wan, Guan, Xin-Yuan
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Australia Ivyspring International Publisher Pty Ltd 2019 Ivyspring International Publisher
Témata:	1-Phosphatidylinositol 3-kinase AKT protein Antibodies Biopsy Blotting, Western Carcinogenesis Carcinogens Cdc42 protein Cell Adhesion Molecules - genetics Cell Adhesion Molecules - metabolism Cell cycle Cell Cycle Checkpoints - genetics Cell Cycle Checkpoints - physiology Cell growth Cell Line Cell Movement - genetics Cell Movement - physiology CHL1 protein Chromosome 3 Chromosome deletion Chromosomes Clonal deletion Committees Deactivation DNA Methylation - genetics DNA Methylation - physiology Ectopic expression Esophagus Filopodia Fluorescent Antibody Technique Gene expression Genes Human subjects Humans Immunoprecipitation Inactivation Integrin beta1 - metabolism Lamellipodia Lung cancer Markers Mesenchyme Metastases Metastasis Nasopharyngeal carcinoma Nasopharyngeal Carcinoma - genetics Nasopharyngeal Carcinoma - metabolism Neurofibromin 2 - metabolism Pathogenesis Promoter Regions, Genetic - genetics Proto-Oncogene Proteins c-akt - metabolism Rac1 protein Real-Time Polymerase Chain Reaction Research Paper RhoA protein RNA Interference Signal transduction Signal Transduction - genetics Signal Transduction - physiology Signaling Survival Tumor suppressor genes Tumors Hong Kong China St Louis Missouri United States > US China Germany nasopharyngeal carcinoma tumor metastasis tumor suppressor gene tumor invasion
ISSN:	1449-2288, 1449-2288
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Shrnutí:	Deletion of Chromosome 3p is one of the most frequently detected genetic alterations in nasopharyngeal carcinoma (NPC). We reported the role of a novel 3p26.3 tumor suppressor gene (TSG) in NPC. Down-regulation of was detected in 4/6 of NPC cell lines and 71/95 (74.7%) in clinical tissues. Ectopic expressions of CHL1 in NPC cells significantly inhibit colony formation and cell motility in functional study. By up-regulating epithelial markers and down-regulating mesenchymal markers could induce mesenchymal-epithelial transition (MET), a key step in preventing tumor invasion and metastasis. could also cause the inactivation of RhoA/Rac1/Cdc42 signaling pathway and inhibit the formation of stress fiber, lamellipodia, and filopodia. could co-localize with adhesion molecule Integrin-β1, the expression of was positively correlated with Integrin-β1 and another known tumor suppressor gene (TSG) Merlin. Down-regulation of Integrin-β1 or Merlin was significantly correlated with the poor survival rate of NPC patients. Further mechanistic studies showed that could directly interact with integrin-β1 and link to Merlin, leading to the inactivation of integrin β1-AKT pathway. In conclusion, is a vital tumor suppressor in the carcinogenesis of NPC.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Competing Interests: The authors have declared that no competing interest exists.
ISSN:	1449-2288 1449-2288
DOI:	10.7150/ijbs.34785