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高磷酸甘油酸脱氢酶表达诱导甲状腺癌的干性和侵袭性。

High Phosphoglycerate Dehydrogenase Expression Induces Stemness and Aggressiveness in Thyroid Cancer.

机构信息

Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Asan Institute of Life Science, Asan Medical Center, Seoul, Korea.

出版信息

Thyroid. 2020 Nov;30(11):1625-1638. doi: 10.1089/thy.2020.0105. Epub 2020 Jun 26.

Abstract

We examined the changes in glucose metabolites of papillary thyroid cancer (PTC) and identified phosphoglycerate dehydrogenase (PHGDH) as a potential target. The role of in the proliferation and tumorigenesis of thyroid cancer cells and its clinical significance were analyzed. Glucose metabolites of various thyroid tissues were analyzed via targeted metabolomics analysis. experiments using s, inhibitor (NCT503), or overexpression in thyroid cell lines (BCPAP, 8505C, and Nthy-Ori) were performed. experiments were performed by using . Human tissue samples and The Cancer Genome Atlas (TCGA) data were used to validate the experimental findings. knockdown in BCPAP and 8505c cell lines significantly inhibited cell viability, colony formation, and tumor spheroid formation compared with the control. In addition, treatment with NCT503 showed similar results. inhibition by both knockdown and treatment with NCT503 significantly inhibited the expression of embryonic cancer stemness markers (, , , and ). overexpression in Nthy-Ori cells significantly increased cell viability and colony formation. The stemness markers were significantly increased after overexpression. knockdown significantly inhibited tumor growth in an mouse xenograft study using 8505c cells. The protein expression of Oct4 in tumors was significantly reduced after knockdown. The associations between expression and stemness markers were confirmed in the TCGA data and human thyroid tissue samples. Positive PHGDH protein expression was associated with metastases of PTC. expression is induced in thyroid cancer and is associated with stemness and aggressiveness of PTC.

摘要

我们研究了甲状腺乳头癌(PTC)的葡萄糖代谢物变化,并确定磷酸甘油酸脱氢酶(PHGDH)为潜在靶点。分析了在甲状腺癌细胞增殖和致瘤中的作用及其临床意义。通过靶向代谢组学分析分析了各种甲状腺组织的葡萄糖代谢物。在甲状腺细胞系(BCPAP、8505C 和 Nthy-Ori)中使用 siRNA、抑制剂(NCT503)或过表达进行了实验。使用 Western blot 进行了实验。使用人组织样本和癌症基因组图谱(TCGA)数据验证了实验结果。与对照组相比,BCPAP 和 8505c 细胞系中 的敲低显着抑制了细胞活力、集落形成和肿瘤球体形成。此外,NCT503 的治疗也显示出类似的结果。通过敲低和 NCT503 治疗的抑制均显着抑制了胚胎癌干性标志物(、、、和)的表达。Nthy-Ori 细胞中过表达显着增加了细胞活力和集落形成。过表达后,干性标志物显着增加。在使用 8505c 细胞的 小鼠异种移植研究中, 的敲低显着抑制了肿瘤生长。 的敲低显着降低了肿瘤中 Oct4 的蛋白表达。在 TCGA 数据和人甲状腺组织样本中证实了 表达与干性标志物之间的关联。PHGDH 蛋白表达阳性与 PTC 的转移有关。在甲状腺癌中表达上调,与 PTC 的干性和侵袭性有关。

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