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Lasp1 promotes malignant phenotype of non-small-cell lung cancer via inducing phosphorylation of FAK-AKT pathway.

ABSTRACT: Lasp1 (LIM and SH3 domain protein 1) promotes tumor proliferation and invasion in multiple cancer entities including non-small cell lung cancer (NSCLC). However, the molecular mechanism is uncertain to date. In the present study, using immunohistochemistry, we found that Lasp1 expression was significantly correlated with tumor size (P=0.005), advanced TNM stage (P=0.042), positive regional lymph node metastasis (P=0.034) and poor overall survival (P<0.001). Similar results were seen in patients with squamous cell lung carcinoma (P=0.003 for larger tumor size, P=0.017 for advanced TNM stage, P=0.003 for positive lymph node metastasis and P<0.001 for poor overall survival) but not in patients with lung adenocarcinoma (P>0.05). Proliferation and invasion assay showed that Lasp1 dramatically promoted the ability of proliferation and invasion of NSCLC cells. Subsequent western blot results revealed that Lasp1 promoted the expression of Cyclin A2, CyclinB1, and Snail, and inhibited the expression of E-cadherin. Lasp1 directly interacted with FAK and facilitated the expression of phosphorylated FAK (Tyr397) and AKT (Ser473). Incorporation of both FAK inhibitor and AKT inhibitor counteracted the upregulating expression of Cyclin A2, CyclinB1, and Snail, and downregulating expression of E-cadherin expression induced by Lasp1 overexpression. Interestingly, inhibition of FAK signaling pathway attenuated the phosphorylation of AKT, but inhibition of AKT signaling pathway did not affect the phosphorylation of FAK. In conclusion, Lasp1 facilitated tumor proliferation and invasion of NSCLC through directly binding to FAK and enhancing the phosphorylation of FAK (Tyr397) and AKT (Ser473). Lasp1 may be a novel therapeutic target in the treatment of NSCLC patients.

SUBMITTER: Zhang X

PROVIDER: S-EPMC5650404 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Lasp1 promotes malignant phenotype of non-small-cell lung cancer via inducing phosphorylation of FAK-AKT pathway.

Zhang Xiupeng X Liu Yang Y Fan Chuifeng C Wang Liang L Li Ailin A Zhou Haijing H Cai Lin L Miao Yuan Y Li Qingchang Q Qiu Xueshan X Wang Enhua E

Oncotarget 20170824 43

Lasp1 (LIM and SH3 domain protein 1) promotes tumor proliferation and invasion in multiple cancer entities including non-small cell lung cancer (NSCLC). However, the molecular mechanism is uncertain to date. In the present study, using immunohistochemistry, we found that Lasp1 expression was significantly correlated with tumor size (P=0.005), advanced TNM stage (P=0.042), positive regional lymph node metastasis (P=0.034) and poor overall survival (P<0.001). Similar re ...[more]

PMID: 29088849

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Lasp1 promotes malignant phenotype of non-small-cell lung cancer via inducing phosphorylation of FAK-AKT pathway.

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Lasp1 promotes malignant phenotype of non-small-cell lung cancer via inducing phosphorylation of FAK-AKT pathway.

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