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首页> 外文期刊>Cellular Physiology and Biochemistry >CHK2 Promotes Anoikis and is Associated with the Progression of Papillary Thyroid Cancer
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CHK2 Promotes Anoikis and is Associated with the Progression of Papillary Thyroid Cancer

机译：CHK2促进神经过敏，并与乳头状甲状腺癌的进展有关。

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Background/Aims Cell cycle checkpoint kinase 2 (CHK2) performs essential cellular functions and might be associated with tumorigenesis and tumor progression. Here, we explored the function and molecular mechanisms of CHK2 in the progression of papillary thyroid cancer (PTC). Methods The expression levels of both total CHK2 and activated CHK2 (p-CHK2) in tissues from 100 PTC patients were detected and evaluated using immunohistochemistry. The roles of CHK2 on cell proliferation, invasion, migration, apoptosis and cancer stem cell (CSC) markers were investigated by CCK-8, Transwell, flow cytometry, western blot and ALDEFLOUR assay. PTC cells cultured in suspension conditions were assayed for anoikis. The anchorage-independent condition was further detected by soft agar colony formation assay. Furthermore, anoikis associated regulatory proteins were explored by western blot and verified by forced downregulation experiment, respectively. Results We found that the levels of both CHK2 and p-CHK2 were significantly upregulated in PTC cancer tissues compared with those in tumor-adjacent tissues. The overexpression of p-CHK2 in primary tumor tissues was associated with tumor aggressiveness and metastatic potential. However, the levels of both CHK2 and p-CHK2 were decreased in metastatic lymph nodes. Our results showed that CHK2 upregulated the levels of CSC markers with no effect on cell proliferation, invasion and migration. Interestingly, we revealed a previously undescribed anoikis-promoting role for CHK2 in PTC. Specifically, the detachment of PTC cells from the extracellular matrix (ECM) triggers CHK2 degradation. Then, the forced downregulation of CHK2 rescued PTC cells from anoikis, but no effect was observed on the apoptosis of adherent PTC cells. Additionally, as a novel regulator of anoikis, CHK2 can induce cell death in a p53-independent manner via the regulation of PRAS40 activation. Conclusion High expression levels of CHK2 and p-CHK2 were associated with the progression of PTC. Our results defined an unexpected role for CHK2 as a mediator of anoikis that functions through the regulation of PRAS40 activation, which may be associated with the survival of circulating tumor cells and metastatic behavior.
机译：背景/目的细胞周期检查点激酶2（CHK2）执行重要的细胞功能，可能与肿瘤发生和肿瘤进展有关。在这里，我们探讨了CHK2在甲状腺乳头状癌（PTC）进展中的功能和分子机制。方法检测100例PTC患者组织中总CHK2和活化CHK2（p-CHK2）的表达水平，并进行免疫组化分析。通过CCK-8，Transwell，流式细胞仪，western blot和ALDEFLOUR试验研究了CHK2在细胞增殖，侵袭，迁移，凋亡和癌症干细胞（CSC）标记中的作用。测定在悬浮条件下培养的PTC细胞的缺氧。通过软琼脂菌落形成试验进一步检测了不依赖于锚定的状况。此外，通过蛋白质印迹探索了与神经相关的调节蛋白，并通过强制下调实验对其进行了验证。结果我们发现与癌旁组织相比，PTC癌组织中CHK2和p-CHK2的水平均显着上调。 p-CHK2在原发性肿瘤组织中的过表达与肿瘤的侵袭性和转移潜力有关。但是，转移性淋巴结中CHK2和p-CHK2的水平均降低。我们的结果表明，CHK2上调了CSC标记的水平，而对细胞增殖，侵袭和迁移没有影响。有趣的是，我们揭示了CHK2在PTC中先前未描述的促进阳极氧化的作用。具体而言，PTC细胞与细胞外基质（ECM）的分离会触发CHK2降解。然后，强制下调CHK2从anokis中拯救了PTC细胞，但未观察到对贴壁PTC细胞凋亡的影响。另外，作为一种新型的神经调节剂，CHK2可以通过调节PRAS40激活以p53独立的方式诱导细胞死亡。结论CHK2和p-CHK2的高表达与PTC的进展有关。我们的结果定义了CHK2作为神经调节剂的意外作用，其通过调节PRAS40激活发挥功能，这可能与循环肿瘤细胞的存活和转移行为有关。

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