TAGLN2 promotes papillary thyroid carcinoma invasion via the Rap1/PI3K/AKT axis.

Abstract

TAGLN2, an actin-binding protein, functions as a binding protein to actin to facilitate the formation of intracellular cytoskeleton structures. TAGLN2 overexpression in papillary thyroid carcinoma (PTC) is reported in our previous study. This study aimed to examine the functions and molecular mechanisms of TAGLN2 in PTC. The clinical data analysis showed that TAGLN2 expression was associated with cervical lymph node metastasis in PTC. Gain- and loss-of-function approaches, as well as various cellular function, gene expression profiles, quantitative proteomics, and molecular biology experiments, were further exploited to explore the roles of TAGLN2 in PTC. The results showed that TAGLN2 overexpression significantly promoted the invasion of PTC cell lines (K1, TPC-1, and BCPAP). Besides, the results also indicated that TAGLN2 was associated with regulating proliferation, migration, angiogenesis, and adhesion of PTC cells. Gene expression profile, quantitative proteomics, and Western blotting were performed to identify the relevant pathways and key downstream molecules, and Rap1/PI3K/AKT signalling pathway, ITGB5, LAMC2, CRKL, vimentin, N-cadherin, and E-cadherin were finally focused on. Moreover, rescue experiments validated the involvement of the Rap1/PI3K/AKT signalling pathway in the TAGLN2-mediated invasion of PTC cells. Therefore, TAGLN2 may promote the invasion of PTC cells via the Rap1/PI3K/AKT signalling pathway and may be served as a potential therapeutic target for PTC. Developing antagonists targeting TAGLN2 may be a potentially effective therapeutic strategy for PTC.