title: Inhibiting β-catenin expression promotes efficiency of radioiodine treatment in aggressive follicular thyroid cancer cells probably through mediating NIS localization.
abstract: The present study investigated whether the efficacy of radioiodine therapy towards aggressive thyroid cancer cells was affected by β-catenin activity and associated with sodium/iodine symporter (NIS) localization. Human thyroid cancer cell line follicular thyroid carcinoma (FTC) 133 was endowed with aggressiveness by HIF-1α or β-catenin overexpression. The protein amount and subcellular localization of NIS, and the radioiodine uptake capacity were detected in the cells, as well as in cells subsequently undergoing β-catenin knockdown. Xenograft experiments were conducted to compare the tumor growth ability and responsiveness to radioactive treatment among HIF-1α and β-catenin overexpressing FTC cells, respectively with or without β-catenin knockdown. β-catenin increased upon HIF-1α overexpression, but not vice versa. This signal axis would prompt metastatic propensity in FTC cells, and translocate NIS from cytomembrane to cytoplasm. Consistently the radioiodine uptake capacity in the cells decreased obviously. Knockdown of β-catenin reversed all these changes. Furthermore, the xenograft experiments showed that radioiodine treatment could thoroughly suppress tumor growth ability of aggressive FTC cells only if the HIF-1α-induced β-catenin activation was disrupted by β-catenin knockdown. β-catenin nuclear translocation in tumor cells was accompanied by abnormal subcellular localization of NIS. Moreover, we found that only after inhibiting β-catenin expression, can the radioiodine treatment promote apoptosis other than repress proliferation and survival in xenograft tumor cells. In conclusion, aggressive FTC cells overexpressing HIF-1α will be fully cracked down by radioiodine therapy once β-catenin expression is inhibited, and regulated localization of NIS may account for underlying mechanisms.
authors.affiliation: Department of Endocrinology, Beijing Jishuitan Hospital, Beijing 100035, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lan
authors.affiliation: Department of Genitourinary, Cancer Medicine, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA.
authors.forename: Spyros
authors.initials: S
authors.lastname: Basourakos
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Dai
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Genitourinary, Cancer Medicine, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Department of Endocrinology, Beijing Jishuitan Hospital, Beijing 100035, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Endocrinology, Beijing Jishuitan Hospital, Beijing 100035, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Huo
authors.affiliation: Department of Endocrinology, Beijing Jishuitan Hospital, Beijing 100035, P.R. China.
authors.forename: Linghai
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Beijing Jishuitan Hospital, Beijing 100035, P.R. China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Beijing Jishuitan Hospital, Beijing 100035, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Bingyin
authors.initials: B
authors.lastname: Shi
authors.affiliation: Department of Genitourinary, Cancer Medicine, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Luo
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D011836:Radiation Tolerance / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects; D027981:Symporters / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D051176:beta Catenin; D000099209:Sodium-Iodide Symporters