CHL1 suppresses tumor growth and metastasis in nasopharyngeal carcinoma by repressing PI3K/AKT signaling pathway via interaction with Integrin β1 and Merlin
| Autor: | Jin Na Chen, Qian Chen, Li Yi Zhang, Sai Wah Tsao, Xin Yuan Guan, Yan Qun Xiang, Hong Tang, Cai Lei Zhu, Dora L.W. Kwong, Chen Jiang, Juan Chen, Ming Liu, Li Fu, Wai Man Liu, Chao Chen, Ling Xi Jiang, Bo Wang |
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| Rok vydání: | 2019 |
| Předmět: |
RHOA
Tumor suppressor gene Integrin RAC1 medicine.disease_cause Applied Microbiology and Biotechnology CHL1 03 medical and health sciences medicine tumor suppressor gene Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology 0303 health sciences tumor metastasis biology nasopharyngeal carcinoma Cell Biology tumor invasion medicine.disease Merlin (protein) Nasopharyngeal carcinoma biology.protein Cancer research Carcinogenesis Research Paper Developmental Biology |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| DOI: | 10.7150/ijbs.34785 |
| Popis: | 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) CHL1 in NPC. Down-regulation of CHL1 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 CHL1 could induce mesenchymal-epithelial transition (MET), a key step in preventing tumor invasion and metastasis. CHL1 could also cause the inactivation of RhoA/Rac1/Cdc42 signaling pathway and inhibit the formation of stress fiber, lamellipodia, and filopodia. CHL1 could co-localize with adhesion molecule Integrin-β1, the expression of CHL1 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 CHL1 could directly interact with integrin-β1 and link to Merlin, leading to the inactivation of integrin β1-AKT pathway. In conclusion, CHL1 is a vital tumor suppressor in the carcinogenesis of NPC. |
| Databáze: | OpenAIRE |
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