TAGLN and High-mobility Group AT-Hook 2 (HMGA2) Complex Regulates TGF-β-induced Colorectal Cancer Metastasis

Background: Colorectal cancer is one of the three most common cancers worldwide. Altered TGF-beta signaling pathway in colorectal cancer is associated with metastasis and poor prognosis. It is also involved in epithelial-to-mesenchymal transition (EMT), which is essential in progression and metastasis. This study aims to investigate the role of transgelin (TAGLN) and high-mobility group AT-hook 2 (HMGA2) in the progression of colon cancer. Methods: HT29 and HCT116 cells were treated with TGF-beta, and the effects of inhibition of TAGLN and overexpression of HMGA2 on TGF-beta treated cell on cell migration and invasion, expression of EMT markers, including E-cadherin, vimentin and fibronectin were detected as well as MMP2 and MMP9, which are critical in cancer cell metastasis. The interaction of TAGLN and HMGA2 was also investigated by using co-immunoprecipitation. The function of TAGLN in tumor metastasis and growth was investigated in vivo. Results: We found that TGF-beta could significantly promote the migration of HT29 and HCT116 cells, as well as TAGLN protein expression and nucleus translocation, while inhibition of TAGLN could effectively reverse the effects of TGF-beta on HT29 and HCT116 cells, which was observed in terms of decreased cell migration and invasion. Knockdown of TAGLN could also rescue TGF-beta-induced loss of E-cadherin, and decreased TGF-beta-induced vimentin and fibronectin expression; the elevation of MMP9 and MMP2 was also reversed by inhibition of TAGLN. Further investigation confirmed the interaction of HMGA2 and TAGLN, as overexpression of HMGA2 restores the effects of TGF-beta on HT29 cells, which were attenuated by TAGLN inhibition both in vitro and in vivo. Conclusion: Overall, our study revealed that interaction between TAGLN and HMGA2 was involved in TGF-beta-induced cell migration and promotion of colon cancer cells, suggesting that HMGA2 and TAGLN are potential molecular targets to prevent colon cancer progression.