hMTH1 is required for maintaining migration and invasion potential of human thyroid cancer cells
hMTH1 is required for maintaining migration and invasion potential of human thyroid cancer cells
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DOI：
10.1016/j.dnarep.2018.07.006
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发表时间：
2018-09-01
期刊：
影响因子：
3.8
通讯作者：
Czarnocka, Barbara
中科院分区：
文献类型：
--
作者：
Arczewska, Katarzyna D.;Stachurska, Anna;Czarnocka, Barbara
癌细胞，包括甲状腺癌细胞，遭受氧化应激损害多个细胞靶点，如DNA和核苷酸池。人突变同源物1(HMTH1)通过净化氧化的DNA前体8-oxodGTP的核苷酸池来控制DNA氧化损伤负荷。已有研究表明，hMTH1对肿瘤细胞的增殖和存活至关重要，因此，抑制hMTH1已被提出为一种新的抗癌治疗策略。在这里，我们发现甲状腺癌细胞对siRNA介导的hMTH1缺失有反应，DNA损伤负荷增加，增殖率适度降低，但没有检测到凋亡、细胞周期停滞或衰老。然而，重要的是，hMTH1缺失显著降低了甲状腺癌细胞的迁移和侵袭潜力。因此，我们的结果允许我们提出hMTH1可能是甲状腺恶性肿瘤的一个治疗靶点，特别是在控制转移方面。
Cancer cells, including thyroid cancer cells, suffer from oxidative stress damaging multiple cellular targets, such as DNA and the nucleotide pool. The human MutT homologue 1 (hMTH1) controls the oxidative DNA damage load by sanitizing the nucleotide pool from the oxidized DNA precursor, 8-oxodGTP. It has previously been shown that hMTH1 is essential for cancer cell proliferation and survival, therefore hMTH1 inhibition has been proposed as a novel anticancer therapeutic strategy. Here we show that thyroid cancer cells respond to siRNA mediated hMTH1 depletion with increased DNA damage load and moderately reduced proliferation rates, but without detectable apoptosis, cell-cycle arrest or senescence. Importantly, however, hMTH1 depletion significantly reduced migration and invasion potential of the thyroid cancer cells. Accordingly, our results allow us to propose that hMTH1 may be a therapeutic target in thyroid malignancy, especially for controlling metastasis.