IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma
Abstract Background Thyroid cancer is the most common malignant endocrine tumor and is classified into papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) and anaplastic thyroid cancer (ATC), which have substantially different characteristics. Insulin-like growth factor binding protein 7...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-06-01
|
| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13578-019-0310-2 |
| _version_ | 1818995071465291776 |
|---|---|
| author | Le Zhang Rong Lian Jingjing Zhao Xianming Feng Runyi Ye Lingxiao Pan Jueheng Wu Mengfeng Li Yongbo Huang Junchao Cai |
| author_facet | Le Zhang Rong Lian Jingjing Zhao Xianming Feng Runyi Ye Lingxiao Pan Jueheng Wu Mengfeng Li Yongbo Huang Junchao Cai |
| author_sort | Le Zhang |
| collection | DOAJ |
| description | Abstract Background Thyroid cancer is the most common malignant endocrine tumor and is classified into papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) and anaplastic thyroid cancer (ATC), which have substantially different characteristics. Insulin-like growth factor binding protein 7 (IGFBP7) has recently been recognized as a tumor suppressor in many cancer types. However, the expression pattern of IGFBP7 and its biological function in various types of thyroid carcinoma remain poorly understood. Results We found that the protein levels of IGFBP7 in FTC and ATC tissues were significantly lower or even absent compared with those in normal thyroid, benign thyroid adenoma and classical PTC tissues. Moreover, overexpression of IGFBP7 in two undifferentiated ATC cell lines, ARO and FRO, and one differentiated FTC cell line, WRO, significantly inhibited cell proliferation in vitro. In vivo experiments revealed that ectopic IGFBP7 expression markedly suppressed growth of tumor xenografts derived from these thyroid cancer cell lines, while IGFBP7 silencing accelerated tumor growth. At the mechanistic level, overexpression of IGFBP7 dramatically suppressed phosphorylation-mediated activation and kinase activity of AKT, causing an upregulation of cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p21Cip1 and induction of G1/S cell cycle arrest, while silencing IGFBP7 exerted the opposite effects. Conclusions IGFBP7 expression is decreased or even absent in FTC and ATC. Acting as a cell cycle repressor, IGFBP7 plays an important tumor-suppressive role in human thyroid cancer, especially in FTC and ATC subtypes and may represent a promising biomarker and therapeutic target for human thyroid cancer treatment. |
| first_indexed | 2024-12-20T21:08:01Z |
| format | Article |
| id | doaj.art-6ff9cbf2d6e24d608f57e72f9c046192 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-12-20T21:08:01Z |
| publishDate | 2019-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-6ff9cbf2d6e24d608f57e72f9c0461922022-12-21T19:26:34ZengBMCCell & Bioscience2045-37012019-06-019111310.1186/s13578-019-0310-2IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinomaLe Zhang0Rong Lian1Jingjing Zhao2Xianming Feng3Runyi Ye4Lingxiao Pan5Jueheng Wu6Mengfeng Li7Yongbo Huang8Junchao Cai9Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen UniversityKey Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen UniversityDepartment of Cardiology, The First Affiliated Hospital, Sun Yat-sen UniversityKey Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen UniversityDepartment of Breast and Thyroid Surgery, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Guangzhou Medical UniversityKey Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen UniversityKey Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen UniversityState Key Laboratory of Respiratory Diseases and Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical UniversityKey Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-sen UniversityAbstract Background Thyroid cancer is the most common malignant endocrine tumor and is classified into papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) and anaplastic thyroid cancer (ATC), which have substantially different characteristics. Insulin-like growth factor binding protein 7 (IGFBP7) has recently been recognized as a tumor suppressor in many cancer types. However, the expression pattern of IGFBP7 and its biological function in various types of thyroid carcinoma remain poorly understood. Results We found that the protein levels of IGFBP7 in FTC and ATC tissues were significantly lower or even absent compared with those in normal thyroid, benign thyroid adenoma and classical PTC tissues. Moreover, overexpression of IGFBP7 in two undifferentiated ATC cell lines, ARO and FRO, and one differentiated FTC cell line, WRO, significantly inhibited cell proliferation in vitro. In vivo experiments revealed that ectopic IGFBP7 expression markedly suppressed growth of tumor xenografts derived from these thyroid cancer cell lines, while IGFBP7 silencing accelerated tumor growth. At the mechanistic level, overexpression of IGFBP7 dramatically suppressed phosphorylation-mediated activation and kinase activity of AKT, causing an upregulation of cyclin-dependent kinase (CDK) inhibitors p27Kip1 and p21Cip1 and induction of G1/S cell cycle arrest, while silencing IGFBP7 exerted the opposite effects. Conclusions IGFBP7 expression is decreased or even absent in FTC and ATC. Acting as a cell cycle repressor, IGFBP7 plays an important tumor-suppressive role in human thyroid cancer, especially in FTC and ATC subtypes and may represent a promising biomarker and therapeutic target for human thyroid cancer treatment.http://link.springer.com/article/10.1186/s13578-019-0310-2IGFBP7Thyroid cancerCell cycleAKTProliferation |
| spellingShingle | Le Zhang Rong Lian Jingjing Zhao Xianming Feng Runyi Ye Lingxiao Pan Jueheng Wu Mengfeng Li Yongbo Huang Junchao Cai IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma Cell & Bioscience IGFBP7 Thyroid cancer Cell cycle AKT Proliferation |
| title | IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma |
| title_full | IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma |
| title_fullStr | IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma |
| title_full_unstemmed | IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma |
| title_short | IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma |
| title_sort | igfbp7 inhibits cell proliferation by suppressing akt activity and cell cycle progression in thyroid carcinoma |
| topic | IGFBP7 Thyroid cancer Cell cycle AKT Proliferation |
| url | http://link.springer.com/article/10.1186/s13578-019-0310-2 |
| work_keys_str_mv | AT lezhang igfbp7inhibitscellproliferationbysuppressingaktactivityandcellcycleprogressioninthyroidcarcinoma AT ronglian igfbp7inhibitscellproliferationbysuppressingaktactivityandcellcycleprogressioninthyroidcarcinoma AT jingjingzhao igfbp7inhibitscellproliferationbysuppressingaktactivityandcellcycleprogressioninthyroidcarcinoma AT xianmingfeng igfbp7inhibitscellproliferationbysuppressingaktactivityandcellcycleprogressioninthyroidcarcinoma AT runyiye igfbp7inhibitscellproliferationbysuppressingaktactivityandcellcycleprogressioninthyroidcarcinoma AT lingxiaopan igfbp7inhibitscellproliferationbysuppressingaktactivityandcellcycleprogressioninthyroidcarcinoma AT juehengwu igfbp7inhibitscellproliferationbysuppressingaktactivityandcellcycleprogressioninthyroidcarcinoma AT mengfengli igfbp7inhibitscellproliferationbysuppressingaktactivityandcellcycleprogressioninthyroidcarcinoma AT yongbohuang igfbp7inhibitscellproliferationbysuppressingaktactivityandcellcycleprogressioninthyroidcarcinoma AT junchaocai igfbp7inhibitscellproliferationbysuppressingaktactivityandcellcycleprogressioninthyroidcarcinoma |