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

• Published in: International journal of biological sciences Vol. 15; no. 9; pp. 1802 - 1815
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 2019; Ivyspring International Publisher
• Subjects: 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
• DOI: 10.7150/ijbs.34785

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.