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Overexpression of glucocorticoid receptor promotes the poor progression and induces cisplatin resistance through p38 MAP kinase in cervical cancer patients

Authors
 Gwan Hee Han  ;  Hee Yun  ;  Julie Kim  ;  Joon-Yong Chung  ;  Jae-Hoon Kim  ;  Hanbyoul Cho 
Citation
 AMERICAN JOURNAL OF CANCER RESEARCH, Vol.12(7) : 3437-3454, 2022-07 
Journal Title
AMERICAN JOURNAL OF CANCER RESEARCH
ISSN
 2156-6976 
Issue Date
2022-07
Keywords
FoxP3 ; Glucocorticoid receptor ; biomarker ; cervical cancer ; cisplatin resistance
Abstract
Glucocorticoid receptor (GR) is activated by synthetic glucocorticoid or endogenous cortisol which were released by the physical and psychosocial stress, and recent studies reported that it is involved in tumor initiation and metastasis in various solid cancers. However, role of GR in cervical cancer has not been elucidated yet. Therefore, here we aim to unveil the role of GR in cervical cancer with cervical cancer clinical specimen and cervical cancer cell lines. We found that overexpression of GR was associated with poor prognosis in cervical cancer patients. Also, GR knockdown in cervical cancer cell lines showed diminished proliferation, invasion and EMT properties. Besides, we found that GR was positively associated with FoxP3 expression, and combination of GR and FoxP3 overexpression revealed as more reliable biomarker for poor prognosis and poor response to chemotherapy of cervical cancer patient than GR alone. Moreover, FACS-based Annexin-V/PI double staining and cleavage of poly ADP ribose polymerase (PARP) showed that siGR enhanced cisplatin-induced apoptosis, which was mediated by p38 MAP kinase. Collectively, our findings established that the combination of high GR and FoxP3 was associated with cervical cancer progression and platinum resistance, suggesting a potential predictive biomarker for clinical management in patients with cervical cancer.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Hoon(김재훈) ORCID logo https://orcid.org/0000-0001-6599-7065
Yun, Hee(윤희)
Cho, Hanbyoul(조한별) ORCID logo https://orcid.org/0000-0002-6177-1648
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191634
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