文章：

SRC酪氨酸激酶与Podoplanin在Entosis过程中的作用分析

Analysis of the Role of the SRC Tyrosine Kinase and Podoplanin in the Process of Entosis

原文发布日期：29 September 2025

DOI: 10.3390/cancers17193173

类型: Article

开放获取: 是

英文摘要：

Background: Over the last years, the phenomenon of entosis, a form of cell-in-cell structure, has been highlighted in various tumors, including poorly treatable breast or pancreatic cancers. Nevertheless, not only the biological properties, but also the molecular drivers of entosis remain unclear. Here, we evaluated SRC tyrosine kinase, a key proto-oncogene, and podoplanin (PDPN), a membrane glycoprotein, as potential regulators of entotic cell formation. Methods: In the study, two entosis-competent cell lines, BxPC-3 and MFC-7, originating from pancreatic and breast cancers, respectively, were used.SRCorPDPNgenes were silenced using dedicated siRNA and the frequency of entotic structure formation was assessed using fluorescent staining and confocal imaging. Results: It was found that BxPC-3 cells deficient inPDPNare more prone to form entotic structures and that over 90% of all entotic figures formed by mixed PDPN+and PDPN-BxPC-3 cells involvedPDPN-silenced cells. The SRC data supports this observation, as the suppressed entotic formation ability presented bySRC-deficient cells was linked with increased expression ofPDPN. Even though the observed effects were mainly limited to BxPC-3 cells, asPDPNexpression in MCF-7 cells is restricted, overall, the obtained data suggest a strong anti-entotic function of PDPN. Additionally, the performed Western blotting indicated the activation of ezrin-radixin-moesin (ERM) proteins inPDPN-deficient cells. Conclusions: Taken together, these data suggest that the negatively controlled PDPN-ERM axis may act as a molecular factor controlling the development of entotic structures and cells with naturally lowPDPNexpression may be more liable to form entoses.

摘要翻译： 

背景：近年来，细胞套叠结构的一种形式——内吞作用现象，已在多种肿瘤中被凸显，包括难以治疗的乳腺癌或胰腺癌。然而，不仅其生物学特性，内吞作用的分子驱动因素也尚不明确。本研究评估了SRC酪氨酸激酶（一种关键的原癌基因）和podoplanin（PDPN，一种膜糖蛋白）作为内吞细胞形成的潜在调节因子。方法：研究中使用了两种具有内吞能力的细胞系，分别源自胰腺癌的BxPC-3和乳腺癌的MCF-7。通过专用siRNA沉默SRC或PDPN基因，并利用荧光染色和共聚焦成像评估内吞结构形成的频率。结果：研究发现，缺乏PDPN的BxPC-3细胞更容易形成内吞结构，并且由PDPN+和PDPN- BxPC-3细胞混合形成的所有内吞结构中，超过90%涉及PDPN沉默的细胞。SRC数据支持这一观察，因为SRC缺陷细胞表现出的内吞形成能力受抑制与PDPN表达增加相关。尽管观察到的效应主要限于BxPC-3细胞（因为MCF-7细胞中PDPN表达受限），但总体而言，获得的数据表明PDPN具有强大的抗内吞功能。此外，进行的Western印迹分析显示，在PDPN缺陷细胞中ezrin-radixin-moesin（ERM）蛋白被激活。结论：综上所述，这些数据表明，负向调控的PDPN-ERM轴可能作为控制内吞结构发展的分子因素，而天然低表达PDPN的细胞可能更容易形成内吞结构。

原文链接：

Analysis of the Role of the SRC Tyrosine Kinase and Podoplanin in the Process of Entosis