RRC ID 63511
著者 Shimada H, Satohisa S, Kohno T, Takahashi S, Hatakeyama T, Konno T, Tsujiwaki M, Saito T, Kojima T.
タイトル The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in malignancy of human endometrial cancer cells.
ジャーナル Oncotarget
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.
巻・号 7(19)
ページ 27735-52
公開日 2016-5-10
DOI 10.18632/oncotarget.8408
PII 8408
PMID 27036040
PMC PMC5053684
MeSH Adiponectin / metabolism Berberine / pharmacology Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Down-Regulation Endometrial Neoplasms / pathology* Endometrium / cytology Endometrium / pathology Epithelial Cells / metabolism Female Gene Knockdown Techniques Humans Hypoglycemic Agents / pharmacology* Leptin / metabolism MARVEL Domain Containing 2 Protein / metabolism* Metformin / pharmacology Neoplasm Invasiveness RNA Interference RNA, Small Interfering Receptors, Lipoprotein / genetics Receptors, Lipoprotein / metabolism* Risk Factors Tight Junctions / metabolism* Transcription Factors / genetics Transcription Factors / metabolism*
IF 5.168
リソース情報
ヒト・動物細胞 Sawano(RCB1152)