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KIF5B-RET fusion kinase promotes cell growth by multilevel activation of STAT3 in lung cancer.


ABSTRACT: BACKGROUND:Lung cancer in nonsmokers tends to be driven by a single somatic mutation or a gene fusion. KIF5B-RET fusion is an oncogene identified in non-small cell lung cancers. In this study, we verified the oncogenic activity of KIF5B-RET fusion and investigated how KIF5B-RET activates the specific signaling pathways for cellular transformation. We aimed to provide a basis for the further development of the therapy for KIF5B-RET positive lung cancer patients. METHODS:RT-PCR was used to screen for KIF5B-RET fusions in Chinese lung cancer patients. To verify the oncogenic activity of KIF5B-RET kinase in lung cancer cells, we manipulated its expression genetically followed by colony formation and tumor formation assays. The mechanism by which KIF5B-RET kinase induces proliferation was investigated by western blot, coimmunoprecipitation, and administration of RET, MAPK and STAT3 inhibitors. RESULTS:Our study identified a KIF5B-RET fusion in Chinese NSCLC patients and demonstrated that KIF5B-RET transfected cells showed a significantly increased proliferation rate and colony-forming ability. Furthermore, we found that KIF5B-RET fusion kinase induced multilevel activation of STAT3 at both Tyr705 and Ser727, and KIF5B-RET-STAT3 signaling related inhibitors repressed the proliferation and tumorigenicity of lung cancer cells significantly. CONCLUSIONS:Our data suggest that KIF5B-RET promotes the cell growth and tumorigenicity of non-small cell lung cancers through multilevel activation of STAT3 signaling, providing possible strategies for the treatment of KIF5B-RET positive lung cancers.

SUBMITTER: Qian Y 

PROVIDER: S-EPMC4114102 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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KIF5B-RET fusion kinase promotes cell growth by multilevel activation of STAT3 in lung cancer.

Qian YingYing Y   Chai Shoujie S   Liang Zuyu Z   Wang Yongfang Y   Zhou You Y   Xu Xia X   Zhang Chenchen C   Zhang Min M   Si Jingxing J   Huang Feiteng F   Huang Zhangdan Z   Hong Wei W   Wang Kai K  

Molecular cancer 20140721


<h4>Background</h4>Lung cancer in nonsmokers tends to be driven by a single somatic mutation or a gene fusion. KIF5B-RET fusion is an oncogene identified in non-small cell lung cancers. In this study, we verified the oncogenic activity of KIF5B-RET fusion and investigated how KIF5B-RET activates the specific signaling pathways for cellular transformation. We aimed to provide a basis for the further development of the therapy for KIF5B-RET positive lung cancer patients.<h4>Methods</h4>RT-PCR was  ...[more]

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