title: Protocadherin 10 inhibits cell proliferation and induces apoptosis via regulation of DEP domain containing 1 in endometrial endometrioid carcinoma.
abstract: Endometrial cancer is the most common gynecologic malignancy and about 80% of these cancers are endometrial endometrioid carcinoma (EEC). Previously, we have demonstrated that protocadherin 10 (PCDH10) is a tumor suppressor gene in EEC, and in this study we further explored the molecular mechanisms of PCDH10 in EEC. We first detect the PCDH10 expression in EEC tissues and then investigate the mechanism in two EEC cell lines. The mRNA and protein expression levels were measured by quantitative real time PCR (qRT-PCR) and western blot, respectively; Cell growth was determined by MTS, CCK-8 and colony formation assays; Cell cycle was determined by flow cytometry, and cell apoptosis was examined by flow cytometry and TUNEL assay. The downstream mediator of PCHD10 was confirmed by Topflash luciferase reporter assay. QRT-PCR and western blot results showed that PCDH10 was down-regulated in EEC clinical tissues. Restoration of PCDH10 suppressed cell growth and induced apoptosis in EEC cells. Dishevelled, EGL-10 and Pleckstrin domain containing 1 (DEPDC1) was a potential downstream mediator of PCDH10 as revealed by RNA-sequencing, and mechanistic studies suggested that DEPDC1 is a downstream mediator and promotes cell growth and induces apoptosis in EEC cells. Western blot further showed that PCDH10 restoration activate apoptotic signaling pathway via caspase signaling in both EEC cell lines and EEC clinical tissues. Collectively, our results suggest that PCDH10-DEPDC1-caspase signaling may be a novel regulatory axis in EEC development and it will be of great interest to explore the clinical significance of PCDH10 and DEPDC1 in the future.
authors.affiliation: Reproductive Medicine Center of the Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China. Electronic address: yangyihua@glmc.edu.cn.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology of the Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China. Electronic address: 260070985@qq.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology of the Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China. Electronic address: jiangmanman@126.com.
authors.forename: Man
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Reproductive Medicine Center of the Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China. Electronic address: zhangxq1006@163.com.
authors.forename: Jiamiao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology of the Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China. Electronic address: 1224462833@qq.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology of the Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China. Electronic address: shelittle@163.com.
authors.forename: Yuanping
authors.initials: Y
authors.lastname: She
authors.affiliation: Reproductive Medicine Center of the Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China. Electronic address: 854777399@qq.com.
authors.forename: Wanxue
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Shatin, N. T., Hong Kong Special Administrative Region. Electronic address: shrilly@cuhk.edu.hk.
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Obstetrics and Gynecology of the Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China. Electronic address: glyy169@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ye
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D000091363:Protocadherins; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015820:Cadherins; C584411:DEPDC1 protein, human; D020690:GTPase-Activating Proteins; D009363:Neoplasm Proteins; C438603:PCDH10 protein, human; D000091363:Protocadherins; D020169:Caspases
keywords: Apoptosis; Caspase; Cell growth; DEPDC1; EEC; PCDH10