Objective:To explore whether cytoplasmic linker protein 170(CLIP170)affects papillary thyroid cancer(PTC)cell metastasis and invasion and clarify the underlying mechanisms.Methods:We analyzed CLIP170 expression levels in PTC using GEO and TCGA data and con-structed CLIP170 knockdown(CLIP170KD)cells using lentiviral transfection.Then,we evaluated their functions through Transwell transfer and invasion assays.We assessed how CLIP170 affected the cellular actin structure via immunofluorescence analysis.We detected transforming growth factor-β 1(TGF-β1)release in the cell culture medium using enzyme-linked immunosorbent assay(ELISA).We also assessed epithelial-mesenchymal transition(EMT)and TGF-β signaling pathway molecule expression using immunoblotting and reverse-transcription quantitat-ive fluorescence PCR and validated the results in a nude mouse lung metastasis model.Results:CLIP170 expression level in PTC was lower than that in normal thyroid tissue.Regarding the function,CLIP170KD significantly enhanced PTC cell metastasis both in vitro and in vivo.Re-garding the underlying mechanism,CLIP170KD triggered TGF-β pathway activation,subsequently promoted tumor cell migration and invasion.The inhibitor of TGF-β effectively inhibited TGF-β activation,and this inhibition significantly reversed the CLIP170KD-induced tumor metastasis.Conclusions:CLIP170 could be a promising therapeutic target to mitigate metastatic tendencies in PTC.