SIRT6/HIF-1α axis promotes papillary thyroid cancer progression by inducing epithelial-mesenchymal transition

• Published in: Cancer cell international Vol. 19; no. 1; p. 17
• Main Authors: Yang, Zhou, Yu, Weiping, Huang, Renhong, Ye, Min, Min, Zhijun
• Format: Journal Article
• Language: English
• Published: England BioMed Central 16.01.2019; BMC
• Subjects: Cell adhesion & migration; Cell migration; Cell proliferation; Colorectal cancer; E-cadherin; Epithelial–mesenchymal transition; Hypoxia; Hypoxia inducible factor-1α; Immunofluorescence; Immunoglobulins; Kinases; Lung cancer; Lymphocytes B; Mesenchyme; Metabolism; Metastasis; Pancreatic cancer; Papillary thyroid cancer; Primary Research; Prostate cancer; Protein biosynthesis; Proteins; Sirtuin 6; Sirtuins; Thyroid cancer; Transcription factors; Tumors; Vimentin; Western blotting; Wound healing; United States > US; Sirtuins; Epithelial–mesenchymal transition; Hypoxia inducible factor-1α; Papillary thyroid cancer; Sirtuin 6
• ISSN: 1475-2867; 1475-2867
• DOI: 10.1186/s12935-019-0730-4

In our previous study, we demonstrated that Sirtuin 6 (SIRT6) is upregulated and associated with papillary thyroid cancer (PTC) progression (Qu et al. in Int J Oncol 50(5):1683-92, 2017). This study examined whether SIRT6 promotes epithelial-mesenchymal transition (EMT) of papillary thyroid cancer through hypoxia inducible factor-1α (HIF-1α). SIRT6-upregulated TPC-1 and B-CPAP cells were generated by lentivirus. Western blotting, RT-qPCR, immunofluorescence was performed to detect the following EMT associated markers: E-cadherin, Vimentin, Snail, and TWIST. Cell proliferation was detected by CCK8, and cell invasion and migration were detected by transwell and wound healing assays, respectively. HIF-1α expression was further detected by western blotting in both normoxia and hypoxia conditions. A HIF-1α inhibitor was then used to block HIF-1α expression in SIRT6-upregulated PTC cells. The same parameters were then assessed and compared with control HIF-1α cells. E-cadherin was significantly decreased, whereas Vimentin, Snail, and TWIST were increased in SIRT6-upregulated PTC cells. Additionally, SIRT6 promoted the invasion and migration of PTC cells. We found that SIRT6 enhanced HIF-1α stability and synthesis and prolonged the protein half-life. The changes in the EMT associated markers and in the invasion and migration ability were rescued after inhibition of HIF-1α expression. Furthermore, we found that SIRT6 increased PTC resistance to HIF-1α inhibitor-mediated proliferation changes. These results confirm that the SIRT6/HIF-1α axis promotes papillary thyroid cancer progression by inducing EMT.