Tetraiodothyroacetic acid and transthyretin silencing inhibit pro-metastatic effect of L-thyroxin in anoikis-resistant prostate cancer cells through regulation of MAPK/ERK pathway

Abstract

Prostate cancer is one of the most common malignancies in adult males and metastasis is the leading cause of death cases without satisfactory treatment options. Anoikis-resistance and migration are crucial aspects for the metastasis of various human cancer cells including prostate cancer and L-thyroxin (T4) has been proved to play vital roles in tumor metastasis. The present study demonstrated that T4 promoted migration and depressed detachment-induced apoptosis in anoikis-resistant prostate cancer cells while tetraiodothyroacetic acid (tetrac), a competitive antagonist of T4 at integrin αvβ3, reversed T4 induced effects through diminishing expressions of XIAP, MMP-2, VEGF together with inhibited activity of MAPK/ERK pathway. In addition, we illustrated that over-expression of transthyretin (TTR) was positively correlated to the progression and metastatic potential in prostate cancer. Similar to tetrac, TTR silencing also inverted T4 mediated bioeffects on anoikis-resistant PC-3 cells. The current study sheds light on novel therapeutic strategies for metastatic prostate cancer.

Implications: This study identified novel compound and target for preventing metastasis in anoikis-resistant prostate cancer cells, which might offer potential therapeutic alternatives for advanced prostate cancer.

Keywords: Anoikis; Migration; Prostate cancer; Tetrac; Thyroxin; Transthyretin.