PINX1 promotes malignant transformation of thyroid carcinomas through AKT, MAPK, and β‐catenin signaling activation

Abstract

Although a large proportion of thyroid cancers, specifically papillary thyroid carcinomas (PTCs), generally show indolent biological behavior, some patients present with aggressive clinical manifestations such as distant metastasis and recurrence. It was also shown that PTC could be progressed to more malignant subtype, anaplastic thyroid carcinomas (ATCs), through specific gene mutation and signaling activation. However, the key modulators regulating malignant transformation of PTCs still remain to be identified. In the current study, we found that PIN2/TERF1 interacting telomerase inhibitor 1 (PINX1) was highly expressed in ATC patient tissues and cell lines compared to PTC patient tissues and cell lines. To investigate the effects of PINX1 on proliferation and migration, we checked colony formation capacity, cell migration, and EMT markers expression after regulation of PINX1 expression. Knockout of PINX1 using specific siRNAs decreases cell proliferation and inhibits cell cycle progression in ATC cell lines, whereas PINX1 gene transfection increases cell proliferation and promotes cell cycle progression in PTC cell lines. Moreover, downregulation of PINX1 in ATC cells reduces cell migration and EMT‐related markers expression, while upregulation of PINX1 in PTC cells increases cell migration and EMT‐related markers expression. To verify whether PINX1 is involved in anaplastic progression, we investigated AKT, MAPK, and β‐catenin signaling activation which were reported to play major roles in anaplastic progression of thyroid carcinomas. Decrease of PINX1 expression repressed the phosphorylation of AKT, p38, and ERK and reduced the expression level of β‐catenin in ATC cell lines. Moreover, increase of PINX1 expression promoted the phosphorylation of AKT, p38, and ERK and upregulated the expression level of β‐catenin in PTC cell lines. These results showed that PINX1 might promote cell proliferation, migration and anaplastic progression of thyroid carcinomas through the activation of AKT, MAPK, and β‐catenin signaling pathways.Support or Funding InformationThis study was supported by a grant from the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by the Ministry of Science and ICT (MSIT), Republic of Korea. (No. 50476‐2018)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.