Sunitinib induces primary ectopic endometrial cell apoptosis through up‐regulation of STAT1 in vitro

Li, Jiajie; Abudula, Maidinaimu; Fan, Xiaodan; Wang, Furong; Chen, Yichen; Liu, Liping

doi:10.1002/jcla.23482

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…In recent years, studies have found that STAT1 may act as a tumor promoter (39), suggesting that the function of STAT1 might change with the cellular and external environment (40). Elevation of p-STAT1 has previously been reported to promote apoptosis of ectopic endometrial stromal cells (41). We found that the effect of HK2 on cell proliferation was partially dependent on p-STAT1.…”

Section: Discussionsupporting

confidence: 55%

Down-Regulating Hexokinase 2 Inhibits Proliferation of Endometrial Stromal Cells Through a Noncanonical Pathway Involving Phosphorylated-STAT1 in Endometriosis

Hou¹,

Lei²,

Peng³

et al. 2021

Preprint

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Background: Endometriosis is a benign gynecologic disease that causes chronic pelvic pain, dysmenorrhea and infertility and shares several characteristics with malignant tumors, afflicting women of reproductive age. Hexokinase 2 (HK2) plays a pivotal role as the first rate-limiting enzyme in the metabolic glycolysis pathway, and its abnormal elevation in tumors is associated with tumor genesis and metastasis. However, the expression and role of HK2 in endometriosis remain unclear.Methods: We sequenced the primary endometrial stromal cells from patients with endometrioma and adopted immunohistochemistry, quantitative real-time PCR and western blot to determine the expression of HK2. Then wound healing assays, cell invasion assays, cell proliferation assays were performed to explore the functions of HK2 in endometrial stromal cells. Furthermore, mice models of endometriosis were recruited to observe the effects of HK2 inhibitors in vivo. Lastly, glycolysis metabolism detection and transcriptome sequencing were carried out in HK2-knockdown endometrial stromal cells to analyze the mechanism of HK2 affecting cell function.Results: Endometriotic stromal cells displayed active glycolysis metabolism and elevated expression of HK2. Downregulating HK2 reduced the migration, invasion and proliferation capacity of endometrial stromal cells. Knockdown of HK2 induced upregulation of signal transducer and activator of transcription 1 (STAT1) and their phosphorylation to attenuate the proliferation of endometrial stromal cells.Conclusions: HK2 was associated with the migration, invasion and proliferation of endometrial stromal cells, which might provide new insights into the pathogenesis and treatment of endometriosis.

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Section: Discussionsupporting

confidence: 55%

Down-Regulating Hexokinase 2 Inhibits Proliferation of Endometrial Stromal Cells Through a Noncanonical Pathway Involving Phosphorylated-STAT1 in Endometriosis

Hou¹,

Lei²,

Peng³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In this context, Li et al [38] showed that the upregulation of caspase-3 expression is concomitant with and correlated to the expression of the signal transducer and activator of transcription 1 (STAT1), which is also an important signal molecule in inflammatory response modulation. In addition, in a study of the potential beneficial effect of Kuntai Capsule (KTC) on apoptosis, Zhong et al [39] showed that the modulation of caspase-8, caspase-9, caspase-3, and cytochrome could promote apoptosis in the EMS tissues.…”

Section: Apoptosis and Emsmentioning

confidence: 99%

Molecular and Clinical Insights on the Complex Interaction between Oxidative Stress, Apoptosis, and Endobiota in the Pathogenesis of Endometriosis

et al. 2021

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Endometriosis (EMS) remains, to date, an intriguing and debilitating gynecological disorder that possesses a multifactorial substrate. Recent studies with the objective of elucidating its etiology highlighted the antagonistic effect of EMS on a multiple of processes involved in homeostasis. Although the current oxidative biomarkers clearly reveal the consequences induced by EMS, its implication in the associated inflammatory reactions could be much more complex. Besides the overproduction of reactive oxygen species (ROS) that leads to an exacerbated oxidative response, it also changes the normal expression of several pro-inflammatory modulators, reflected by the fluctuating activity of several pro- and anti-apoptotic mediators whose expression is impaired. In light of this topic, several studies elucidate the involvement of apoptosis in EMS, being brought controversial findings, even reports with no significant change. Further, some authors reported an abnormal expression of multiple genes that are crucial for the overall functionality of the female reproductive system. Cumulatively, it seems that the subsequent oxidative imbalance and apoptosis process impairment could further disrupt the normal removal of unnecessary biological products. Based on all gathered evidence, we could argue that the related stress state could determine human endobiota impairment, which could further participate in the inflammatory and main antioxidant enzyme changes occurring in EMS. Moreover, a correlation between endobiota integrity, inflammation, and oxidative stress (OS) was suggested in relation to the possible predisposition to pathogen determined infections.

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Downregulating HK2 inhibits proliferation of endometrial stromal cells through a noncanonical pathway involving phosphorylation of signal transducer and activator of transcription 1 in endometriosis

Hou

Lei

Peng

et al. 2022

Biology of Reproduction

View full text Add to dashboard Cite

Background: Endometriosis is a benign gynecologic disease that causes chronic pelvic pain, dysmenorrhea and infertility and shares several characteristics with malignant tumors, afflicting women of reproductive age. Hexokinase 2 (HK2) plays an essential role as the first rate-limiting enzyme in the metabolic glycolysis pathway, and its abnormal elevation in tumors is associated with tumor genesis and metastasis. However, the expression and role of HK2 in endometriosis remain unclear. Methods: We sequenced the primary endometrial stromal cells from patients with endometrioma and utilized immunohistochemistry, quantitative real-time PCR and western blot to determine the expression of HK2. Then wound healing assays, cell invasion assays, cell proliferation assays were performed to explore the functions of HK2 in endometrial stromal cells. Furthermore, mice models of endometriosis were used to observe the effects of HK2 inhibitors in vivo. Lastly, glycolysis metabolism detection and transcriptome sequencing were carried out in HK2-knockdown endometrial stromal cells to analyze the mechanism of HK2 affecting cell function. Results: Endometrial stromal cells of endometrioma displayed active glycolysis metabolism and elevated expression of HK2. Downregulating HK2 reduced the migration, invasion and proliferation capacity of endometrial stromal cells. Knockdown of HK2 induced upregulation of signal transducer and activator of transcription 1 (STAT1) and their phosphorylation to attenuate the proliferation of endometrial stromal cells. Conclusions: HK2 is associated with the migration, invasion and proliferation of endometrial stromal cells, which might provide new insights into the pathogenesis and treatment of endometriosis.

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Sunitinib induces primary ectopic endometrial cell apoptosis through up‐regulation of STAT1 in vitro

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 3 publications

References 24 publications

Down-Regulating Hexokinase 2 Inhibits Proliferation of Endometrial Stromal Cells Through a Noncanonical Pathway Involving Phosphorylated-STAT1 in Endometriosis

Down-Regulating Hexokinase 2 Inhibits Proliferation of Endometrial Stromal Cells Through a Noncanonical Pathway Involving Phosphorylated-STAT1 in Endometriosis

Molecular and Clinical Insights on the Complex Interaction between Oxidative Stress, Apoptosis, and Endobiota in the Pathogenesis of Endometriosis

Downregulating HK2 inhibits proliferation of endometrial stromal cells through a noncanonical pathway involving phosphorylation of signal transducer and activator of transcription 1 in endometriosis

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