Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kong, Deguang, Li, Anping, Liu, Yu, Cui, Qiuxia, Wang, Kun, Zhang, Dan, Tang, Jianing, Du, Yaying, Liu, Zhisu, Wu, Gaosong, Wu, Kongming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933607/
https://www.ncbi.nlm.nih.gov/pubmed/31921695
http://dx.doi.org/10.3389/fonc.2019.01450
_version_ 1783483240085979136
author Kong, Deguang
Li, Anping
Liu, Yu
Cui, Qiuxia
Wang, Kun
Zhang, Dan
Tang, Jianing
Du, Yaying
Liu, Zhisu
Wu, Gaosong
Wu, Kongming
author_facet Kong, Deguang
Li, Anping
Liu, Yu
Cui, Qiuxia
Wang, Kun
Zhang, Dan
Tang, Jianing
Du, Yaying
Liu, Zhisu
Wu, Gaosong
Wu, Kongming
author_sort Kong, Deguang
collection PubMed
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.
format Online
Article
Text
id pubmed-6933607
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-69336072020-01-09 SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1 Kong, Deguang Li, Anping Liu, Yu Cui, Qiuxia Wang, Kun Zhang, Dan Tang, Jianing Du, Yaying Liu, Zhisu Wu, Gaosong Wu, Kongming Front Oncol Oncology 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. Frontiers Media S.A. 2019-12-20 /pmc/articles/PMC6933607/ /pubmed/31921695 http://dx.doi.org/10.3389/fonc.2019.01450 Text en Copyright © 2019 Kong, Li, Liu, Cui, Wang, Zhang, Tang, Du, Liu, Wu and Wu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Kong, Deguang
Li, Anping
Liu, Yu
Cui, Qiuxia
Wang, Kun
Zhang, Dan
Tang, Jianing
Du, Yaying
Liu, Zhisu
Wu, Gaosong
Wu, Kongming
SIX1 Activates STAT3 Signaling to Promote the Proliferation of Thyroid Carcinoma via EYA1
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 Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933607/
https://www.ncbi.nlm.nih.gov/pubmed/31921695
http://dx.doi.org/10.3389/fonc.2019.01450
work_keys_str_mv AT kongdeguang six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1
AT lianping six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1
AT liuyu six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1
AT cuiqiuxia six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1
AT wangkun six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1
AT zhangdan six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1
AT tangjianing six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1
AT duyaying six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1
AT liuzhisu six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1
AT wugaosong six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1
AT wukongming six1activatesstat3signalingtopromotetheproliferationofthyroidcarcinomaviaeya1