Targeted therapies in thyroid cancer

Capdevila, Jaume; Peréz-García, José Manuel; Obiols, Gabriel; Tabernero, Josep

doi:10.1007/s11523-009-0124-y

Cited by 2 publications

(1 citation statement)

References 62 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have demonstrated that STAT3 is required for efficient cellular transformation by an array of well-characterized oncogenes including EGFR [20], RAS [21], ALK [22], and even RET related oncogenes such as RET-MEN2A/2B [23], RET-FMTC [24] and RET/PTC [25,26]. Phosphorylation on the Ser 727 residue enhances the transcriptional activity of STAT3.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

View full text Add to dashboard Cite

BackgroundLung 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.MethodsRT-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.ResultsOur 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.ConclusionsOur 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.

show abstract