Competition between human cells by entosis  

作　　者：Qiang Sun Tianzhi Luo Yixin Ren Oliver Florey Senji Shirasawa Takehiko Sasazuki Douglas N Robinson Michael Overholtzer 

机构地区：[1]Laboratory of Cell Engineering, Institute of Biotechnology, Beijing 100071, China [2]Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA [3]Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA [4]Signalling Programme, The Babraham Institute, Cambridge, CB22 3AT, UK [5]Department of Cell Biology, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan [6]Department of Pathology, Research Institute, International Medical Center of Japan, Tokyo 163-8655, Japan [7]BCMB Allied Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA

出　　处：《Cell Research》2014年第11期1299-1310,共12页细胞研究（英文版）

基　　金：Acknowledgments We thank Drs Alan Hall, Xuejun Jiang and their lab members and members of the Overholtzer laboratory for reagents and discussions on the manuscript. We thank Drs Keith Burridge, Klaus Hahn, Marilyn Resh and Tingchao Chou for reagents. We thank Drs Elisa de Stanchina, Xiaodong Huang and Juan Qiu for help with animal experiments, and Ms Ning Fan for histology. This work was supported by the NCI （CA154649, MO）, the NIGMS （GM66817, DNR）, the Louis V Gerstner, Jr Young Investigators Fund （MO）, the Benjamin Friedman Research Fund （MO）, Cancer Research UK fellowship （C47718/A16337, OF）, the National Basic Research Program of China （2015CB553704, QS）, and the National Natural Science Foundation of China （30871364 and 81472588, QS）.

摘　　要：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 ceils 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.

关 键 词：entosis cell competition cell cannibalism cell-in-cell structure tumor evolution KRAS Rho GTPase 

分 类 号：Q279[生物学—细胞生物学] TS201.22[轻工技术与工程—食品科学]