Ogihara Takuo, Mizoi Kenta, Kamioka Hiroki, Yano Kentaro
Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, 60, Nakaorui-machi, Takasaki, Gunma 370-0033, Japan.
Faculty of Pharmacy, Takasaki University of Health and Welfare, 60, Nakaorui-machi, Takasaki, Gunma 370-0033, Japan.
Cancers (Basel). 2020 Nov 12;12(11):3352. doi: 10.3390/cancers12113352.
One factor contributing to the malignancy of cancer cells is the acquisition of drug resistance during chemotherapy via increased expression of efflux transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP). These transporters operate at the cell membrane, and are anchored in place by the scaffold proteins ezrin (Ezr), radixin (Rdx), and moesin (Msn) (ERM proteins), which regulate their functional activity. The identity of the regulatory scaffold protein(s) differs depending upon the transporter, and also upon the tissue in which it is expressed, even for the same transporter. Another factor contributing to malignancy is metastatic ability. Epithelial-mesenchymal transition (EMT) is the first step in the conversion of primary epithelial cells into mesenchymal cells that can be transported to other organs via the blood. The SNAI family of transcriptional regulators triggers EMT, and SNAI expression is used is an indicator of malignancy. Furthermore, EMT has been suggested to be involved in drug resistance, since drug excretion from cancer cells is promoted during EMT. We showed recently that ERM proteins are induced by a member of the SNAI family, Snail. Here, we first review recent progress in research on the relationship between efflux transporters and scaffold proteins, including the question of tissue specificity. In the second part, we review the relationship between ERM scaffold proteins and the transcriptional regulatory factors that induce their expression.
癌细胞恶性化的一个促成因素是在化疗期间通过外排转运蛋白（如P-糖蛋白（P-gp）、多药耐药相关蛋白（MRP）和乳腺癌耐药蛋白（BCRP））表达增加而获得耐药性。这些转运蛋白在细胞膜上发挥作用，并由支架蛋白埃兹蛋白（Ezr）、根蛋白（Rdx）和膜突蛋白（Msn）（ERM蛋白）锚定在适当位置，这些蛋白调节它们的功能活性。调节支架蛋白的身份因转运蛋白而异，也因它所表达的组织而异，即使是同一转运蛋白也是如此。促成恶性化的另一个因素是转移能力。上皮-间质转化（EMT）是原发性上皮细胞转化为间充质细胞的第一步，间充质细胞可通过血液转运到其他器官。转录调节因子的SNAI家族触发EMT，SNAI的表达被用作恶性化的指标。此外，EMT被认为与耐药性有关，因为在EMT期间癌细胞的药物排泄会增加。我们最近表明，ERM蛋白是由SNAI家族的一个成员Snail诱导的。在这里，我们首先回顾外排转运蛋白与支架蛋白之间关系的研究进展，包括组织特异性问题。在第二部分中，我们回顾ERM支架蛋白与诱导其表达的转录调节因子之间的关系。
