Pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake
Abstract Previous studies have shown that pyruvate carboxylase (PC) plays a key role in the occurrence and progression of thyroid cancer (TC); however, the relationship between PC and iodine-refractory TC is unclear. Therefore, the present study aimed to investigate the molecular mechanism of PC in...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-10-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-01214-y |
| _version_ | 1828318387970768896 |
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| author | Yang Liu Chang Liu Yu Pan Jinxin Zhou Huijun Ju Yifan Zhang |
| author_facet | Yang Liu Chang Liu Yu Pan Jinxin Zhou Huijun Ju Yifan Zhang |
| author_sort | Yang Liu |
| collection | DOAJ |
| description | Abstract Previous studies have shown that pyruvate carboxylase (PC) plays a key role in the occurrence and progression of thyroid cancer (TC); however, the relationship between PC and iodine-refractory TC is unclear. Therefore, the present study aimed to investigate the molecular mechanism of PC in the malignant progression and loss of iodine uptake in papillary TC (PTC) and to explore the potential therapeutic effect of PC inhibitors in iodine-refractory PTC. PC increased cell proliferation, invasion, and metastasis, inhibited expression of the iodine metabolism-related genes TSHR, NIS, TPO, and TG, and decreased the iodine-uptake capacity by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in PTC cell lines. Furthermore, the PC inhibitor ZY-444 effectively inhibited the activation of PC, reduced the malignant invasiveness, and restored the expression of iodine metabolism-related genes and the iodine-uptake capacity in PTC cells. These findings suggest that PC activation is involved in the progression of iodine-refractory TC and that PC inhibitors may represent a potentially novel targeted therapy for iodine-refractory TC. |
| first_indexed | 2024-04-13T17:41:14Z |
| format | Article |
| id | doaj.art-2ed49eba997a482fa090e7052139fff3 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-13T17:41:14Z |
| publishDate | 2022-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-2ed49eba997a482fa090e7052139fff32022-12-22T02:37:10ZengNature Publishing GroupCell Death Discovery2058-77162022-10-018111310.1038/s41420-022-01214-yPyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptakeYang Liu0Chang Liu1Yu Pan2Jinxin Zhou3Huijun Ju4Yifan Zhang5Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University, School of MedicineDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University, School of MedicineDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University, School of MedicineDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University, School of MedicineDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University, School of MedicineDepartment of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University, School of MedicineAbstract Previous studies have shown that pyruvate carboxylase (PC) plays a key role in the occurrence and progression of thyroid cancer (TC); however, the relationship between PC and iodine-refractory TC is unclear. Therefore, the present study aimed to investigate the molecular mechanism of PC in the malignant progression and loss of iodine uptake in papillary TC (PTC) and to explore the potential therapeutic effect of PC inhibitors in iodine-refractory PTC. PC increased cell proliferation, invasion, and metastasis, inhibited expression of the iodine metabolism-related genes TSHR, NIS, TPO, and TG, and decreased the iodine-uptake capacity by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in PTC cell lines. Furthermore, the PC inhibitor ZY-444 effectively inhibited the activation of PC, reduced the malignant invasiveness, and restored the expression of iodine metabolism-related genes and the iodine-uptake capacity in PTC cells. These findings suggest that PC activation is involved in the progression of iodine-refractory TC and that PC inhibitors may represent a potentially novel targeted therapy for iodine-refractory TC.https://doi.org/10.1038/s41420-022-01214-y |
| spellingShingle | Yang Liu Chang Liu Yu Pan Jinxin Zhou Huijun Ju Yifan Zhang Pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake Cell Death Discovery |
| title | Pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake |
| title_full | Pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake |
| title_fullStr | Pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake |
| title_full_unstemmed | Pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake |
| title_short | Pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake |
| title_sort | pyruvate carboxylase promotes malignant transformation of papillary thyroid carcinoma and reduces iodine uptake |
| url | https://doi.org/10.1038/s41420-022-01214-y |
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