Estrogen regulates PDPK1 to promote cell proliferation in epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is a common estrogen-sensitive tumor that poses a serious threat to women 's health, and the mortality rate of EOC ranks first among malignant tumors in females. Studies have indicated a strong link between estrogen abnormality and EOC progression. We accidently...

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Main Authors: Yajie Wang, Huanchao Chang, Xiuwen Li, Hairong Zhang, Qianqian Zhou, Shengjian Tang, Di Wang
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:Heliyon
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Online Access:http://www.sciencedirect.com/science/article/pii/S240584402416327X
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author Yajie Wang
Huanchao Chang
Xiuwen Li
Hairong Zhang
Qianqian Zhou
Shengjian Tang
Di Wang
author_facet Yajie Wang
Huanchao Chang
Xiuwen Li
Hairong Zhang
Qianqian Zhou
Shengjian Tang
Di Wang
author_sort Yajie Wang
collection DOAJ
description Epithelial ovarian cancer (EOC) is a common estrogen-sensitive tumor that poses a serious threat to women 's health, and the mortality rate of EOC ranks first among malignant tumors in females. Studies have indicated a strong link between estrogen abnormality and EOC progression. We accidently found that 3-phosphoinositide-dependent protein kinase-1 (PDPK1) is highly expressed in EOC tissues. Further, estrogen also up-regulates the expression of PDPK1 in EOC cells. Notably, the expression of PDPK1 is controlled strictly, and its expression can determine the fate of cells. However, to date, the molecular mechanism by which estrogen elicits PDPK1 expression in EOC cells, and the role of PDPK1 in estrogen-driven EOC cells are not well defined. In this research, we found that a high expression of PDPK1 was associated with poor prognosis in patients with ovarian cancer. Further, estrogen stimulated the increase of PDPK1 protein expression through estrogen receptor ESR1. The depletion or overexpression of PDPK1 affected the inhibition or amplification of estrogen-driven EOC cell proliferation, and the knockdown of PDPK1 suppressed the migration of EOC cells by estrogen while promoting cell apoptosis. This suggests a critical functional association between estrogen and PDPK1 in the process of EOC. The expression of messenger RNA for cyclin A1, cyclin-dependent kinase 2 (CDK2), matrix metallopeptidase 2 (MMP2), and bcl-2 associated x protein (Bax) is regulated by PDPK1 under estrogen treatment. Our results indicated that PDPK1 plays a role as an oncogene in the development of EOC; hence, elucidating the mechanism by which estrogen promotes EOC progression by regulating PDPK1 expression.
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spelling doaj-art-cbff67bb61f14dd1bf2d5a69a7c785252024-11-30T07:12:26ZengElsevierHeliyon2405-84402024-11-011022e40296Estrogen regulates PDPK1 to promote cell proliferation in epithelial ovarian cancerYajie Wang0Huanchao Chang1Xiuwen Li2Hairong Zhang3Qianqian Zhou4Shengjian Tang5Di Wang6School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, China; Plastic Surgery Institute, Shandong Second Medical University, Weifang, Shandong 261053, ChinaPlastic Surgery Institute, Shandong Second Medical University, Weifang, Shandong 261053, China; Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, ChinaSchool of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, China; Plastic Surgery Institute, Shandong Second Medical University, Weifang, Shandong 261053, ChinaPlastic Surgery Institute, Shandong Second Medical University, Weifang, Shandong 261053, ChinaAffiliated Hospital of Shandong Second Medical University, Weifang, Shandong, ChinaPlastic Surgery Institute, Shandong Second Medical University, Weifang, Shandong 261053, China; Corresponding author.School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, China; Plastic Surgery Institute, Shandong Second Medical University, Weifang, Shandong 261053, China; Corresponding author. Plastic Surgery Institute, Shandong Second Medical University, Weifang, Shandong, 261053, China.Epithelial ovarian cancer (EOC) is a common estrogen-sensitive tumor that poses a serious threat to women 's health, and the mortality rate of EOC ranks first among malignant tumors in females. Studies have indicated a strong link between estrogen abnormality and EOC progression. We accidently found that 3-phosphoinositide-dependent protein kinase-1 (PDPK1) is highly expressed in EOC tissues. Further, estrogen also up-regulates the expression of PDPK1 in EOC cells. Notably, the expression of PDPK1 is controlled strictly, and its expression can determine the fate of cells. However, to date, the molecular mechanism by which estrogen elicits PDPK1 expression in EOC cells, and the role of PDPK1 in estrogen-driven EOC cells are not well defined. In this research, we found that a high expression of PDPK1 was associated with poor prognosis in patients with ovarian cancer. Further, estrogen stimulated the increase of PDPK1 protein expression through estrogen receptor ESR1. The depletion or overexpression of PDPK1 affected the inhibition or amplification of estrogen-driven EOC cell proliferation, and the knockdown of PDPK1 suppressed the migration of EOC cells by estrogen while promoting cell apoptosis. This suggests a critical functional association between estrogen and PDPK1 in the process of EOC. The expression of messenger RNA for cyclin A1, cyclin-dependent kinase 2 (CDK2), matrix metallopeptidase 2 (MMP2), and bcl-2 associated x protein (Bax) is regulated by PDPK1 under estrogen treatment. Our results indicated that PDPK1 plays a role as an oncogene in the development of EOC; hence, elucidating the mechanism by which estrogen promotes EOC progression by regulating PDPK1 expression.http://www.sciencedirect.com/science/article/pii/S240584402416327XEOCPDPK1EstrogenESR1Oncogene
spellingShingle Yajie Wang
Huanchao Chang
Xiuwen Li
Hairong Zhang
Qianqian Zhou
Shengjian Tang
Di Wang
Estrogen regulates PDPK1 to promote cell proliferation in epithelial ovarian cancer
Heliyon
EOC
PDPK1
Estrogen
ESR1
Oncogene
title Estrogen regulates PDPK1 to promote cell proliferation in epithelial ovarian cancer
title_full Estrogen regulates PDPK1 to promote cell proliferation in epithelial ovarian cancer
title_fullStr Estrogen regulates PDPK1 to promote cell proliferation in epithelial ovarian cancer
title_full_unstemmed Estrogen regulates PDPK1 to promote cell proliferation in epithelial ovarian cancer
title_short Estrogen regulates PDPK1 to promote cell proliferation in epithelial ovarian cancer
title_sort estrogen regulates pdpk1 to promote cell proliferation in epithelial ovarian cancer
topic EOC
PDPK1
Estrogen
ESR1
Oncogene
url http://www.sciencedirect.com/science/article/pii/S240584402416327X
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AT xiuwenli estrogenregulatespdpk1topromotecellproliferationinepithelialovariancancer
AT hairongzhang estrogenregulatespdpk1topromotecellproliferationinepithelialovariancancer
AT qianqianzhou estrogenregulatespdpk1topromotecellproliferationinepithelialovariancancer
AT shengjiantang estrogenregulatespdpk1topromotecellproliferationinepithelialovariancancer
AT diwang estrogenregulatespdpk1topromotecellproliferationinepithelialovariancancer