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 constructed CLIP170 knockdown (CLIP170^KD) 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 quantitative 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, CLIP170^KD significantly enhanced PTC cell metastasis both in vitro and in vivo. Regarding the underlying mechanism, CLIP170^KD 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 CLIP170^KD-induced tumor metastasis.

Conclusions CLIP170 could be a promising therapeutic target to mitigate metastatic tendencies in PTC.