Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer.

Abstract

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.

• Authors: Hiroshi Shimada, Shyuetsu Abe, Takayuki Kohno, Seiro Satohisa, Takumi Konno, Syunta Takahashi, Tsubasa Hatakeyama, Chihiro Arimoto, Takuya Kakuki, Yakuto Kaneko, Ken-Ichi Takano, Tsuyoshi Saito, Takashi Kojima
• Journal: Scientific reports (Sci Rep) Vol. 7 Pg. 37049 (01 10 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28071680 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AMOT protein, human
• AREG protein, human
• Amphiregulin
• Angiomotins
• Cell Cycle Proteins
• DNA-Binding Proteins
• Intercellular Signaling Peptides and Proteins
• LSR protein, human
• Membrane Proteins
• Microfilament Proteins
• Nuclear Proteins
• RNA, Small Interfering
• Receptors, Lipoprotein
• TEA Domain Transcription Factors
• TEAD1 protein, human
• Transcription Factors
• YY1AP1 protein, human

Topics

• Amphiregulin (genetics, metabolism)
• Angiomotins
• Cell Cycle Proteins
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• DNA-Binding Proteins (genetics, metabolism)
• Endometrial Neoplasms (genetics, metabolism)
• Epithelial Cells (physiology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Intercellular Signaling Peptides and Proteins (genetics, metabolism)
• Membrane Proteins (genetics, metabolism)
• Microfilament Proteins
• Nuclear Proteins (genetics, metabolism)
• RNA, Small Interfering (genetics)
• Receptors, Lipoprotein (genetics, metabolism)
• TEA Domain Transcription Factors
• Tight Junctions (metabolism)
• Transcription Factors (genetics, metabolism)