SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1
As a critical member of the Retinal Determination Gene Network (RDGN), SIX1 has been regarded as a tumor promoter in various types of cancer. However, its role in papillary thyroid carcinoma (PTC) has never been investigated. In this study, thyroid carcinoma tissue microarray staining was employed t...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-12-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2019.01450/full |
| _version_ | 1818254444134924288 |
|---|---|
| author | Deguang Kong Anping Li Yu Liu Qiuxia Cui Kun Wang Dan Zhang Jianing Tang Yaying Du Zhisu Liu Gaosong Wu Kongming Wu |
| author_facet | Deguang Kong Anping Li Yu Liu Qiuxia Cui Kun Wang Dan Zhang Jianing Tang Yaying Du Zhisu Liu Gaosong Wu Kongming Wu |
| author_sort | Deguang Kong |
| collection | DOAJ |
| description | As a critical member of the Retinal Determination Gene Network (RDGN), SIX1 has been regarded as a tumor promoter in various types of cancer. However, its role in papillary thyroid carcinoma (PTC) has never been investigated. In this study, thyroid carcinoma tissue microarray staining was employed to identify the expression patterns of SIX1 and its co-activator EYA1. Papillary thyroid cancer cell lines, BCPAP, and TPC-1 cells were used to investigate the potential mechanism of SIX1 in vitro and in vivo. Flow cytometry analysis, MTT assay, the growth curve assay, colony formation assay, EdU incorporation and xenograft assay were performed to demonstrate the role of SIX1 in the malignant change of PTC cells. Western blot and Real-time PCR were used to detect the interaction among the SIX1, EYA1, and STAT3 signaling. In comparison with normal tissue, high expressions of SIX1 and EYA1 were associated with a malignant tumor. Importantly, SIX1 strongly correlated with EYA1 in thyroid carcinoma tissue microarray. Functional assays indicated SIX1 increased EYA1 expression by stabilizing EYA1 at the post-transcriptional level. Besides, SIX1 promoted the proliferation and invasion of thyroid carcinoma via activation of STAT3 signaling and its downstream targets in an EYA1-dependent manner. SIX1 can integrate with EYA1 to contribute to PTC development via activation of the classical STAT3 signaling. These data suggested targeting the abnormal activation of the SIX1/EYA1 complex may represent a novel therapeutic strategy for advanced PTC patients. |
| first_indexed | 2024-12-12T16:56:04Z |
| format | Article |
| id | doaj.art-31f9c235efb44f8187322cb92a453082 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T16:56:04Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-31f9c235efb44f8187322cb92a4530822022-12-22T00:18:13ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2019-12-01910.3389/fonc.2019.01450468842SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1Deguang Kong0Anping Li1Yu Liu2Qiuxia Cui3Kun Wang4Dan Zhang5Jianing Tang6Yaying Du7Zhisu Liu8Gaosong Wu9Kongming Wu10Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, ChinaDepartment of Geriatrics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, ChinaAs a critical member of the Retinal Determination Gene Network (RDGN), SIX1 has been regarded as a tumor promoter in various types of cancer. However, its role in papillary thyroid carcinoma (PTC) has never been investigated. In this study, thyroid carcinoma tissue microarray staining was employed to identify the expression patterns of SIX1 and its co-activator EYA1. Papillary thyroid cancer cell lines, BCPAP, and TPC-1 cells were used to investigate the potential mechanism of SIX1 in vitro and in vivo. Flow cytometry analysis, MTT assay, the growth curve assay, colony formation assay, EdU incorporation and xenograft assay were performed to demonstrate the role of SIX1 in the malignant change of PTC cells. Western blot and Real-time PCR were used to detect the interaction among the SIX1, EYA1, and STAT3 signaling. In comparison with normal tissue, high expressions of SIX1 and EYA1 were associated with a malignant tumor. Importantly, SIX1 strongly correlated with EYA1 in thyroid carcinoma tissue microarray. Functional assays indicated SIX1 increased EYA1 expression by stabilizing EYA1 at the post-transcriptional level. Besides, SIX1 promoted the proliferation and invasion of thyroid carcinoma via activation of STAT3 signaling and its downstream targets in an EYA1-dependent manner. SIX1 can integrate with EYA1 to contribute to PTC development via activation of the classical STAT3 signaling. These data suggested targeting the abnormal activation of the SIX1/EYA1 complex may represent a novel therapeutic strategy for advanced PTC patients.https://www.frontiersin.org/article/10.3389/fonc.2019.01450/fullSIX1EYA1STAT3 signalthyroid papillary carcinomatumor growth |
| spellingShingle | Deguang Kong Anping Li Yu Liu Qiuxia Cui Kun Wang Dan Zhang Jianing Tang Yaying Du Zhisu Liu Gaosong Wu Kongming Wu SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1 Frontiers in Oncology SIX1 EYA1 STAT3 signal thyroid papillary carcinoma tumor growth |
| title | SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1 |
| title_full | SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1 |
| title_fullStr | SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1 |
| title_full_unstemmed | SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1 |
| title_short | SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1 |
| title_sort | six1 activates stat3 signaling to promote the proliferation of thyroid carcinoma via eya1 |
| topic | SIX1 EYA1 STAT3 signal thyroid papillary carcinoma tumor growth |
| url | https://www.frontiersin.org/article/10.3389/fonc.2019.01450/full |
| work_keys_str_mv | AT deguangkong six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1 AT anpingli six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1 AT yuliu six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1 AT qiuxiacui six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1 AT kunwang six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1 AT danzhang six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1 AT jianingtang six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1 AT yayingdu six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1 AT zhisuliu six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1 AT gaosongwu six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1 AT kongmingwu six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1 |