Inhibiting β-catenin expression promotes efficiency of radioiodine treatment in aggressive follicular thyroid cancer cells probably through mediating NIS localization
Inhibiting β-catenin expression promotes efficiency of radioiodine treatment in aggressive follicular thyroid cancer cells probably through mediating NIS localization
复制标题
抑制 β-catenin 表达可能通过介导 NIS 定位提高侵袭性滤泡性甲状腺癌细胞中放射性碘治疗的效率
DOI：
10.3892/or.2016.5228
复制
发表时间：
2017-01-01
期刊：
影响因子：
4.2
通讯作者：
Luo, Yong
中科院分区：
文献类型：
--
作者：
Lan, Ling;Basourakos, Spyros;Luo, Yong
本研究探讨了放射性碘治疗侵袭性甲状腺癌细胞的疗效是否受到β -连环蛋白活性的影响，并与钠/碘同调体（NIS）定位有关。HIF-1 α或β -连环蛋白的过表达使人甲状腺癌细胞滤泡性甲状腺癌（FTC） 133具有侵袭性。在细胞以及随后P-catenin敲除的细胞中检测NIS的蛋白量和亚细胞定位以及放射性碘摄取能力。异种移植实验比较了HIF-1 α和P-catenin过表达的FTC细胞在P-catenin敲低或不敲低时的肿瘤生长能力和对放射性治疗的反应。-连环蛋白随着HIF-1 α的过度表达而增加，反之亦然。该信号轴会促进FTC细胞的转移倾向，并将NIS从细胞膜转移到细胞质。细胞对放射性碘的吸收能力明显下降。p -连环蛋白的下调逆转了所有这些变化。此外，异种移植实验表明，放射性碘治疗可以彻底抑制侵袭性FTC细胞的肿瘤生长能力，只有当HIF-1 α诱导的P-catenin激活被P-catenin敲低而中断。肿瘤细胞中p -连环蛋白核易位伴有异常的NIS亚细胞定位。此外，我们发现放射性碘治疗只有在抑制β -catenin表达后，才能促进异种移植肿瘤细胞的凋亡，而不是抑制肿瘤细胞的增殖和存活。总之，一旦P-catenin表达被抑制，侵袭性FTC细胞过表达HIF-1 α将被放射性碘治疗完全抑制，NIS的调控定位可能解释了潜在的机制。
The present study investigated whether the efficacy of radioiodine therapy towards aggressive thyroid cancer cells was affected by beta-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-1 alpha or beta-catenin over expression. 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 P-catenin knockdown. Xenograft experiments were conducted to compare the tumor growth ability and responsiveness to radioactive treatment among HIF-1 alpha and P-catenin overexpressing FTC cells, respectively with or without P-catenin knockdown. beta-catenin increased upon HIF-1 alpha 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 P-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-1 alpha-induced P-catenin activation was disrupted by P-catenin knockdown. P-catenin nuclear translocation in tumor cells was accompanied by abnormal subcellular localization of NIS. Moreover, we found that only after inhibiting beta-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-1 alpha will be fully cracked down by radio iodine therapy once P-catenin expression is inhibited, and regulated localization of NIS may account for underlying mechanisms.