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CHL1 suppresses tumor growth and metastasis in nasopharyngeal carcinoma by repressing PI3K/AKT signaling pathway via interaction with Integrin ?1 and Merlin.


ABSTRACT: 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-?1, the expression of CHL1 was positively correlated with Integrin-?1 and another known tumor suppressor gene (TSG) Merlin. Down-regulation of Integrin-?1 or Merlin was significantly correlated with the poor survival rate of NPC patients. Further mechanistic studies showed that CHL1 could directly interact with integrin-?1 and link to Merlin, leading to the inactivation of integrin ?1-AKT pathway. In conclusion, CHL1 is a vital tumor suppressor in the carcinogenesis of NPC.

SUBMITTER: Chen J 

PROVIDER: S-EPMC6743306 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Chen Juan J   Jiang Chen C   Fu Li L   Zhu Cai-Lei CL   Xiang Yan-Qun YQ   Jiang Ling-Xi LX   Chen Qian Q   Liu Wai Man WM   Chen Jin-Na JN   Zhang Li-Yi LY   Liu Ming M   Chen Chao C   Tang Hong H   Wang Bo B   Tsao Sai Wah SW   Kwong Dora Lai-Wan DL   Guan Xin-Yuan XY  

International journal of biological sciences 20190711 9


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) <i>CHL1</i> in NPC. Down-regulation of <i>CHL1</i> 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 mesenchyma  ...[more]

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