PMID- 28071680 OWN - NLM STAT- MEDLINE DCOM- 20181022 LR - 20211204 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 DP - 2017 Jan 10 TI - Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer. PG - 37049 LID - 10.1038/srep37049 [doi] LID - 37049 AB - Lipolysis-stimulated lipoprotein receptor (LSR) is a unique molecule of tricellular contacts of normal and cancer cells. We investigated how the loss of LSR induced cell migration, invasion and proliferation in endometrial cancer cell line Sawano. mRNAs of amphiregulin (AREG) and TEA domain family member 1 (TEAD1) were markedly upregulated by siRNA-LSR. In endometrial cancer tissues, downregulation of LSR and upregulation of AREG were observed together with malignancy, and Yes-associated protein (YAP) was present in the nuclei. siRNA-AREG prevented the cell migration and invasion induced by siRNA-LSR, whereas treatment with AREG induced cell migration and invasion. LSR was colocalized with TRIC, angiomotin (AMOT), Merlin and phosphorylated YAP (pYAP). siRNA-LSR increased expression of pYAP and decreased that of AMOT and Merlin. siRNA-YAP prevented expression of the mRNAs of AREG and TEAD1, and the cell migration and invasion induced by siRNA-LSR. Treatment with dobutamine and 2-deoxy-D-glucose and glucose starvation induced the pYAP expression and prevented the cell migration and invasion induced by siRNA-LSR. siRNA-AMOT decreased the Merlin expression and prevented the cell migration and invasion induced by siRNA-LSR. The loss of LSR promoted cell invasion and migration via upregulation of TEAD1/AREG dependent on YAP/pYAP and AMOT/Merlin in human endometrial cancer cells. FAU - Shimada, Hiroshi AU - Shimada H AD - Departments of Obstetrics and Gynecology, University School of Medicine, Sapporo, Japan. AD - Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Abe, Shyuetsu AU - Abe S AD - Departments of Obstetrics and Gynecology, University School of Medicine, Sapporo, Japan. AD - Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Kohno, Takayuki AU - Kohno T AD - Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Satohisa, Seiro AU - Satohisa S AD - Departments of Obstetrics and Gynecology, University School of Medicine, Sapporo, Japan. FAU - Konno, Takumi AU - Konno T AD - Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Takahashi, Syunta AU - Takahashi S AD - Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Hatakeyama, Tsubasa AU - Hatakeyama T AD - Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Arimoto, Chihiro AU - Arimoto C AD - Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. FAU - Kakuki, Takuya AU - Kakuki T AD - Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Departments of Otolaryngology, Sapporo Medical, University School of Medicine, Sapporo, Japan. FAU - Kaneko, Yakuto AU - Kaneko Y AD - Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. AD - Departments of Otolaryngology, Sapporo Medical, University School of Medicine, Sapporo, Japan. FAU - Takano, Ken-Ichi AU - Takano KI AD - Departments of Otolaryngology, Sapporo Medical, University School of Medicine, Sapporo, Japan. FAU - Saito, Tsuyoshi AU - Saito T AD - Departments of Obstetrics and Gynecology, University School of Medicine, Sapporo, Japan. FAU - Kojima, Takashi AU - Kojima T AD - Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170110 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (AMOT protein, human) RN - 0 (AREG protein, human) RN - 0 (Amphiregulin) RN - 0 (Angiomotins) RN - 0 (Cell Cycle Proteins) RN - 0 (DNA-Binding Proteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (LSR protein, human) RN - 0 (Membrane Proteins) RN - 0 (Microfilament Proteins) RN - 0 (Nuclear Proteins) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, Lipoprotein) RN - 0 (TEA Domain Transcription Factors) RN - 0 (TEAD1 protein, human) RN - 0 (Transcription Factors) RN - 0 (YY1AP1 protein, human) SB - IM MH - Amphiregulin/genetics/metabolism MH - Angiomotins MH - Cell Cycle Proteins MH - Cell Line, Tumor MH - Cell Movement MH - Cell Proliferation MH - DNA-Binding Proteins/genetics/metabolism MH - Endometrial Neoplasms/genetics/*metabolism MH - Epithelial Cells/*physiology MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Intercellular Signaling Peptides and Proteins/genetics/metabolism MH - Membrane Proteins/genetics/metabolism MH - Microfilament Proteins MH - Nuclear Proteins/genetics/metabolism MH - RNA, Small Interfering/genetics MH - Receptors, Lipoprotein/genetics/*metabolism MH - TEA Domain Transcription Factors MH - Tight Junctions/*metabolism MH - Transcription Factors/genetics/metabolism PMC - PMC5223122 EDAT- 2017/01/11 06:00 MHDA- 2018/10/23 06:00 PMCR- 2017/01/10 CRDT- 2017/01/11 06:00 PHST- 2016/06/20 00:00 [received] PHST- 2016/10/24 00:00 [accepted] PHST- 2017/01/11 06:00 [entrez] PHST- 2017/01/11 06:00 [pubmed] PHST- 2018/10/23 06:00 [medline] PHST- 2017/01/10 00:00 [pmc-release] AID - srep37049 [pii] AID - 10.1038/srep37049 [doi] PST - epublish SO - Sci Rep. 2017 Jan 10;7:37049. doi: 10.1038/srep37049.