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Abstract
Papillary thyroid cancer (PTC) is the most prevalent histological type of thyroid cancer (TC) worldwide. Although tumor metastasis occurs in regional lymph nodes, distant metastasis (DM) may also occur. Radioactive iodine (RAI) therapy is an effective treatment for TC; however, resistance to RAI occurs in patients with DM. Therefore, in this study, we investigated the efficacy of DM-related biomarkers as therapeutic targets for PTC therapy. ABCA1 expression was higher in aggressive BCPAP cells than in other PTC cells in terms of migration and invasion capacity. The knockdown of ABCA1 substantially decreased the expression of the epithelial-mesenchymal transition (EMT) marker, N-cadherin, and EMT regulator (ZEB1), resulting in suppressed migration and invasion of BCPAP cells. ABCA1 knockdown also reduced ERK activity and Fra-1 expression, which correlated with the effects of an ERK inhibitor or siRNA-mediated inhibition of ERK or Fra-1 expression. Furthermore, ABCA1-knocked-down BCPAP cells suppressed cell migration and invasion by reducing Fra-1 recruitment to Zeb1 promoter; lung metastasis was not observed in mice injected with ABCA1-knocked-down cells. Overall, our findings suggest that ABCA1 regulates lung metastasis in TC cells.

Affiliations

Ji-Hye Park 1 2, Jae-Kyung Myung 1 3, Sun-Joo Lee 4, Hyewon Kim 4, Soyeon Kim 1, Seung-Bum Lee 1, Hyosun Jang 1, Won-Il Jang 1 4, Sunhoo Park 1 4, Hyunwon Yang 5, Sehwan Shim 1, Min-Jung Kim 1
1Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Science, Seoul 01812, Republic of Korea.
2OPTOLANE Technologies Inc., Seongnam 13494, Republic of Korea.
3Department of Pathology, College of Medicine, Hanyang University, Seoul 01812, Republic of Korea.
4Laboratory of Experimental Pathology, Departments of Pathology, Korea Institute of Radiological & Medical Science, Seoul 01812, Republic of Korea.
5Biohealth Convergence, Seoul Women's University, Seoul 01812, Republic of Korea.