title: MPA influences tumor cell proliferation, migration, and invasion induced by RANKL through PRB involving the MAPK pathway in endometrial cancer.
abstract: The targeting of receptor activator of nuclear factor-κB ligand (RANKL) is being increasingly investigated as a potential therapeutic strategy in several types of cancers. However, the exact function and mechanism of RANKL in human endometrial cancer (EC), particularly in progesterone-resistant and aggressive EC, remain unclear. We evaluated whether targeting of RANKL might be an efficient therapeutic strategy in EC. In the present study, we performed the first investigation of the relationship between RANK/RANKL expression in EC tissues and clinicopathological features. In the present study, we showed that RANK/RANKL was aberrantly overexpressed in human EC tissues. The higher RANK expression in human EC was associated with myometrial invasion, lymph node metastasis and lymphovascular space involvement. Additionally, we discovered that RANK/RANKL promoted EC cell proliferation, migration and invasion, which was correlated with the activated mitogen-activated protein kinase (MAPK) pathway. Moreover, medroxyprogesterone acetate (MPA)-mediated progesterone receptor B (PRB) was found to significantly inhibit the EC cell behavior induced by RANKL in vitro. Furthermore, MPA efficiently inhibited the tumorigenicity in an in vivo xenograft model. Collectively, RANKL is a common tumor promoter, which activates MAPK signaling in EC cells. MPA-mediated PRB plays important roles in inhibiting the growth, migratory and invasive capacities of EC cells induced by RANKL. Targeting of RANKL may be useful in the treatment of EC.
authors.affiliation: Department of Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory for Gynecologic Oncology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pathology and Biobank, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gynecology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D009361:Neoplasm Invasiveness; D053245:RANK Ligand / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D018931:Antineoplastic Agents, Hormonal; D053245:RANK Ligand; D011980:Receptors, Progesterone; C097314:progesterone receptor B; D017258:Medroxyprogesterone Acetate