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p190A inactivating mutations cause aberrant RhoA activation and promote malignant transformation via the Hippo-YAP pathway in endometrial cancer

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1792-1803页

作者： Xiaoli Wen Jing Wan Qizhi He Mengfei Wang Shuangdi Li Mei Jiang Zhen Qian Binya Liu Wen Lu Kai Wang Kun Gao Xiaoping Wan Department of Gynecology Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghai 201204China Department of Gynecology International Peace Maternity and Child Health HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Department of Pathology Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghai 201204China Tongji University School of Medicine Shanghai 200092China Clinical and Translational Research Center Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghai 201204China

The Rho family of GTPases is strictly regulated by a large family of GTPase-activating proteins(GAPs)that stimulate the relatively weak intrinsic GTP-hydrolyzing activity of Rho GTPases.p190A is a potent and widely expressed GAP that acts on RhoA GTPases.p190A is frequently mutated in endometrial cancer,but the contribution of p190A mutations to endometrial tumorigenesis remains *** we identified that p190A is an upstream regulator of the Hippo-YAP signaling pathway,which is a critical regulator of cell proliferation,apoptosis,and cell fate.p190A knockout in endometrial cancer cells promoted cell proliferation,migration,and epithelial–mesenchymal transition(EMT),which were partially dependent on YAP ***-type p190A,but not endometrial cancer-associated mutants,suppressed the nuclear localization,transcriptional activity,and malignant transformation function of ***,the nuclear localization of YAP was enhanced in p190A-mutated endometrial *** findings reveal novel molecular mechanisms underlying Hippo-YAP pathway-driven endometrial tumorigenesis and elucidate the potential for therapy targeting the Hippo-YAP pathway in p190A-mutated endometrial cancer.

关键词： endometrial malignant cancer

Clinical significance and role of up-regulation of SERPINA3 expression in endometrial cancer

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World Journal of Clinical Cases 2019年第15期7卷 1996-2002页

作者： Mian-Li Zhou Fang-Shan Chen Hui Mao Department of Gynecology and Obstetrics Traditional Chinese Medicine Hospital Affiliated to Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Department of Oncology Traditional Chinese Medicine Hospital Affiliated to Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina

BACKGROUND Serpin peptidase inhibitor,clade A member 3(SERPINA3)belongs to the serpin family with an inhibitory activity against *** aberrant expression has been observed in a wide range of tumor ***,its clinical significance and biological function in endometrial cancer have been rarely *** designed a study to determine the levels of SERPINA3 and its significance in patients with endometrial *** To investigate the clinical significance and role of SERPINA3 expression in endometrial cancer *** Eighty endometrial tissue samples collected from patients with endometrial cancer were included in an observation group and 80 paraffin-embedded tissues samples collected from patients with normal endometrial tissues undergoing myomectomy were employed as a control group between January 2014 and December *** expression of SERPINA3 mRNA was detected by quantitative polymerase chain reaction(PCR)for all endometrial tissues included in the *** The positive expression rate of SERPINA3 protein in endometrial cancer cells was 71.25%in the observation group,which was significantly higher than that in the control group(31.25%;Pendometrial cancer cells and the age range at which women experienced menopause(P>0.05).However,it was associated with pathological grade,clinical stage,vascular invasion,and lymph node metastasis(Pendometrial *** The follow-up study of SERPINA3 can be used as a prognostic biomarker for endometrial cancer and as one of the targets for bio-targeted therapy for endometrial cancer.

关键词： Serpin peptidase inhibitor,clade A member 3 endometrial cancer Quantitative polymerase chain reaction Expression

Estrogen and insulin synergistically promote endometrial cancer progression via crosstalk between their receptor signaling pathways

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Cancer Biology & Medicine 2019年第1期16卷 55-65页

作者： Wenyan Tian Fei Teng Jinping Gao Chao Gao Guoyan Liu Yanfang Zhang Shizhu Yu Wei Zhang Yingmei Wang Fengxia Xue Department of Gynecology and Obstetrics Tianjin Medical University General Hospital Tianjin Neurological Institute Tianjin Medical University General Hospital Department of Cancer Biology Comprehensive Cancer Center of Wake Forest Baptist Medical Center

Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed ***: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and ***: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in ***: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.

关键词： endometrial cancer(EC) estrogen insulin InsR-β ER-α PI3K/Akt pathway MAPK/ERK pathway

m^(6)A regulator-mediated methylation modification patterns and tumor immune microenvironment characterization in endometrial cancer

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Genes & Diseases 2023年第6期10卷 2278-2281页

作者： Kexin Li Shanrong Shu Jiahua Zou Manmei Li Zhong Liu Guangdong Provincial Key Laboratory of Bioengineering Medicine National Engineering Research Center of Genetic MedicineInstitute of BiomedicineCollege of Life Science and TechnologyJinan UniversityGuangzhouGuangdong 510632China Department of Gynecology and Obstetrics The First Afﬁliated Hospital of Jinan UniversityGuangzhouGuangdong 510630China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) School of PharmacyJinan UniversityGuangzhouGuangdong 510632China

endometrial cancer(EC)is the second most prevalent female reproductive system tumor after cervical cancer and its incidence is rising globally.1 Recently,N6-methyladenosine(m^(6)A)has emerged as an important regulator of a variety of physiological and pathological processes,especially in promoting EC progression.2,3 However,the potential roles of m^(6)A modification in EC and its immune landscape remain ***,the correlation between m^(6)A modification patterns and tumor microenvironment(TME)cell-infiltrating characteristics was comprehensively evaluated based on 21 m^(6)A regulators of 1301 endometrial cancer *** identified four m6Aclasses characterized by distinct TME cell *** used principal component analysis algorithms to construct m6Ascore to quantify m^(6)A modification patterns of endometrial cancer *** results showed that lower m6Ascore may be closely related to immune-inflamed phenotype and displayed immune-activated characteristics and better prognosis.

关键词： endometrial cancer m^(6)A

Advancements in endometrial epithelial stem cell research

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Science China(Life Sciences) 2022年第1期65卷 215-218页

作者： Xiwen Zhang Guangfeng Zhao Yali Hu Nanjing University Medical School Nanjing 210008China Department of Obstetrics and Gynecology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China

The human endometrium is a dynamic tissue that undergoes approximately 400 cycles of proliferation,decidualization,shedding,and *** the observation that superficial stratum functionalis loss and swift reepithelization occur every month,an original hypothesis is that stem cells,especially endometrial epithelial stem cells harbored in the deeper basalis,take on the responsibility of repairing and regenerating the endometrial functionalis.

关键词： endometrial superficial stratum

Correlation between TAMs and proliferation and invasion of type endometrial carcinoma

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Asian Pacific Journal of Tropical Medicine 2015年第8期8卷 632-638页

作者： Hong-Lin Hu Han-Song Bai Hai-Xia Pan Department of Oncology Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Graduate School Zunyi Medical College

Objective: To explore the correlation between tumor-associated macrophages and the proliferation and invasion of type endometrial carcinoma. Methods: Immunohistochemistry was used to investigate the infiltration of macrophages in normal and different types of hyperplastic endometrial lesions. The proliferation and invasion ability of type endometrial carcinoma cell line RL95-2 influenced by mononuclear macrophage cell line THP-1(constructed M2 type macrophages) was detected by CCK8 and transwell technologies respectively. Transwell was used to evaluate the recruiting ability of RL95-2 on THP-1 cells. Otherwise, the western blot was also used to detect the expression of Cyclin D1 and MMP-2 in RL95-2 with the influence of THP-1. Results: Immunohistochemistry result showed a positive correlation between the number of infiltrating macrophages and the progression of endometrial ***-1 recruited by RL95-2 could promote its proliferation and invasion and enhance the expression of the Cyclin D1 and MMP-2 protein in a time dependent manner(Pendometrial carcinoma.

关键词： Tumor-associated macrophages Type endometrial carcinoma Proliferation Invasion

Traction force with extracellular matrix mediated by cytoskeleton influences metastasis through SLC8A1 induced Wnt-b-catenin pathway in endometrial cancer

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Genes & Diseases 2024年第5期11卷 98-101页

作者： Xingchen Li Xin Xu Jianliu Wang Department of Obstetrics and Gynecology Peking University People’s HospitalBeijing 100044China Department of Obstetrics and Gynecology Beijing ChaoYang HospitalCapital Medical UniversityBeijing 100020China

endometrial cancer(EC)is one of the most prominent malignancies in ***,despite these advancements in understanding EC pathogenesis,mortality rates have not *** force(TF)refers to endogenous mechanical forces exerted by cells.1 These forces act on the extracellular matrix and the extracellular tumor microenvironment through focal adhesions,thereby regulating cell proliferation and ***,the TF characteristics of endometrial cancer cells and their heterogeneity remain unclear.

关键词： endometrial metastasis endogenous

Metastatic low-grade endometrial stromal sarcoma with sex cord and smooth muscle differentiation: A case report

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World Journal of Clinical Cases 2019年第2期7卷 221-227页

作者： Qi Zhu Yan-Qin Sun Xiao-Qing Di Bing Huang Jian Huang Center of Pathology Diagnosis and Research Affiliated Hospital of Guangdong Medical University Department of Pathology Guangdong Medical University

BACKGROUND Metastatic low-grade endometrial stromal sarcoma(LG-ESS) with sex cord-like and smooth muscle-like differentiation is rare. This article reports such a case with multiple recurrences and with extensive pelvic and abdominal *** SUMMARY A 47-year-old female patient was diagnosed with multiple cystic masses in the pelvic cavity by magnetic resonance imaging examination. Based on the postoperative pathological and immunohistochemical analyses of the surgical specimen, she was diagnosed with a metastatic low-grade endometrial stromal sarcoma with sex cord and smooth muscle *** LG-ESS is a low-grade malignant tumor with a high recurrence rate and metastasis probability. It is easily misdiagnosed initially. It is essential to distinguish LG-ESS with sex cord-like differentiation from uterine tumour resembling ovarian sex cord tumour.

关键词： endometrial stromal sarcoma Sex cord-like Smooth muscle-like Pathological changes Immunohistochemistry Case report

Analysis of uterine CD49a^(+) NK cell subsets in menstrual blood reflects endometrial status and association with recurrent spontaneous abortion

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Cellular & Molecular Immunology 2021年第7期18卷 1838-1840页

作者： Xianhong Tong Min Gao Xianghui Du Fangting Lu Limin Wu Haiming Wei Binqing Fu The Department of Obstetrics and Gynecology First Affiliated Hospital of University of Science and Technology of ChinaUniversity of Science and Technology of ChinaHefeiChina Anhui Provincial Hospital Affiliated to Anhui Medical University HefeiAnhuiChina Hefei National Laboratory for Physical Sciences at Microscale the CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Institute of Immunology University of Science and Technology of ChinaHefeiChina

Maternal uterine immune cells,especially natural killer(NK)cells,are important for successful pregnancy,and an abnormal number or function of uterine NK cells is closely correlated with an impaired endometrial environment and ***,there are currently no noninvasive testing methods using reliable indicators that accurately predict uterine changes leading to ***,we confirmed that before implantation,menstrual blood(MB)from healthy donors had 70%CD49a^(+)tissue-resident NK(trNK)cells,the majority of which were CD49a^(+)Eomes+NK ***,MB from patients with recurrent spontaneous abortion(RSA)had many fewer CD49a^(+)trNK cells than MB from *** of uNK cell populations in MB may better predict an abnormal endometrial environment associated with miscarriage than peripheral blood(PB)***,we suggest using MB-and CD49a-related markers as a promising noninvasive way to evaluate endometrial status.

关键词： endometrial uterine impaired