title: The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in malignancy of human endometrial cancer cells.
abstract: Lipolysis-stimulated lipoprotein receptor (LSR) has been identified as a novel molecular constituent of tricellular contacts that have a barrier function for the cellular sheet. LSR recruits tricellulin (TRIC), which is the first molecular component of tricellular tight junctions. Knockdown of LSR increases cell motility and invasion of certain cancer cells. However, the behavior and the roles of LSR in endometrial cancer remain unknown. In the present study, we investigated the behavior and roles of LSR in normal and endometrial cancer cells in vivo and in vitro. In endometriosis and endometrial cancer, LSR was observed not only in the subapical region but also throughout the lateral region as well as in normal endometrial epithelial cells in the secretory phase, and LSR in the cancer was reduced in correlation with the malignancy. Knockdown of LSR by the siRNA in cells of the endometrial cancer cell line Sawano, induced cell migration, invasion and proliferation, while TRIC relocalized from the tricellular region to the bicellular region at the membrane. In Sawano cells and normal HEEs, a decrease of LSR induced by leptin and an increase of LSR induced by adiponectin and the drugs for type 2 diabetes metformin and berberine were observed via distinct signaling pathways including JAK2/STAT. In Sawano cells, metformin and berberine prevented cell migration and invasion induced by downregulation of LSR by the siRNA and leptin treatment. The dissection of the mechanism in the downregulation of endometrial LSR during obesity is important in developing new diagnostic and therapy for endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.|Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Seiro
authors.initials: S
authors.lastname: Satohisa
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kohno
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Syunta
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Hatakeyama
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Konno
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tsujiwaki
authors.affiliation: Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000473:pathology*; D004717:Endometrium / Q000166:cytology / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D020738:Leptin / Q000378:metabolism; D062794:MARVEL Domain Containing 2 Protein / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D034741:RNA, Small Interfering; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D019108:Tight Junctions / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D007004:Hypoglycemic Agents; C525854:LSR protein, human; D020738:Leptin; D062794:MARVEL Domain Containing 2 Protein; C516798:MARVELD2 protein, human; D034741:RNA, Small Interfering; D018110:Receptors, Lipoprotein; D014157:Transcription Factors; D001599:Berberine; D008687:Metformin
keywords: LSR; adiponectin; endometrial cancer; leptin; tricellular tight junctions