Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer.
Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer.
复制标题
损失三细胞紧密连接蛋白LSR可通过在人子宫内膜癌中上调TEAD1/AREG促进细胞侵袭和迁移。
DOI：
10.1038/srep37049
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发表时间：
2017-01-10
影响因子：
4.6
通讯作者：
Kojima T
中科院分区：
文献类型：
--
作者：
Shimada H;Abe S;Kohno T;Satohisa S;Konno T;Takahashi S;Hatakeyama T;Arimoto C;Kakuki T;Kaneko Y;Takano KI;Saito T;Kojima T
脂解刺激的脂蛋白受体（LSR）是一种独特的正常细胞和癌细胞的三细胞接触分子。我们研究了LSR的缺失如何诱导子宫内膜癌细胞株Sawano的细胞迁移、侵袭和增殖。双调蛋白（AREG）和TEA结构域家族成员1（TEAD 1）的mRNA被siRNA-LSR显著上调。在子宫内膜癌组织中，LSR表达下调，AREG表达上调，并伴有恶性程度的加重，细胞核中存在Yes相关蛋白（雅普）。siRNA-AREG抑制siRNA-LSR诱导的细胞迁移和侵袭，而AREG处理诱导细胞迁移和侵袭。LSR与TRIC、血管动蛋白（AMOT）、Merlin和磷酸化雅普（p雅普）共定位。siRNA-LSR增加pYAP的表达，降低AMOT和Merlin的表达。siRNA-YAP抑制AREG和TEAD 1基因的表达，抑制siRNA-LSR诱导的细胞迁移和侵袭。多巴酚丁胺和2-脱氧-D-葡萄糖处理以及葡萄糖饥饿诱导pYAP表达，并阻止siRNA-LSR诱导的细胞迁移和侵袭。siRNA-AMOT可抑制siRNA-LSR诱导的细胞迁移和侵袭。LSR的缺失通过上调依赖于雅普/p雅普和AMOT/Merlin的TEAD 1/AREG促进人子宫内膜癌细胞的侵袭和迁移。
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.