Competition between human cells by entosis
Competition between human cells by entosis
复制标题
人体细胞之间通过嵌入竞争
DOI：
10.1038/cr.2014.138
复制
发表时间：
2014-11-01
期刊：
影响因子：
44.1
通讯作者：
Overholtzer, Michael
中科院分区：
文献类型：
--
作者：
Sun, Qiang;Luo, Tianzhi;Overholtzer, Michael
人类癌由已知间接竞争营养物和生长因子的肿瘤细胞的复杂混合物组成。肿瘤细胞是否也可以直接竞争，例如通过消除竞争对手，尚不清楚。在这里，我们表明，人类细胞可以直接竞争的吞噬机制称为entosis。通过内吞，细胞被吞噬，或在活着的时候被吃掉，随后经历细胞死亡。我们发现，吞噬（“赢家”）和吞噬（“输家”）细胞的身份是由RhoA和肌动球蛋白，其中具有高变形能力的肿瘤细胞优先吞噬和竞争的异质群体中的低变形能力的相邻细胞控制的机械变形能力。我们进一步发现激活的Kras和Rac信号通过下调收缩性肌球蛋白赋予细胞赢家地位，允许最终经历细胞死亡的邻近细胞内化。最后，我们计算了细胞中细胞形成的能量景观，证明了赢家和输家细胞之间的机械差异是必要的entosis进行。这些数据定义了在人类肿瘤中发生的哺乳动物细胞中的竞争机制。
Human carcinomas are comprised of complex mixtures of tumor cells that are known to compete indirectly for nutrients and growth factors. Whether tumor cells could also compete directly, for example by elimination of rivals, is not known. Here we show that human cells can directly compete by a mechanism of engulfment called entosis. By entosis, cells are engulfed, or cannibalized while alive, and subsequently undergo cell death. We find that the identity of engulfing (“winner”) and engulfed (“loser”) cells is dictated by mechanical deformability controlled by RhoA and actomyosin, where tumor cells with high deformability preferentially engulf and outcompete neighboring cells with low deformability in heterogeneous populations. We further find that activated Kras and Rac signaling impart winner status to cells by downregulating contractile myosin, allowing for the internalization of neighboring cells that eventually undergo cell death. Finally, we compute the energy landscape of cell-in-cell formation, demonstrating that a mechanical differential between winner and loser cells is required for entosis to proceed. These data define a mechanism of competition in mammalian cells that occurs in human tumors.