Sun Qiang/Wang Xiaoning/Huang Hongyan teamed up to find a new mechanism for cell sleeve death to fight endocal cell genome instability with p53 signals

mitosis is a basic form of division in animal cells, a process that is strictly regulated to ensure the production of normal child cells, which in turn maintains cell replacement and human growth and development. When there is an abnormality of silk division, the cell spindle assembly checkpoint (spindle assemble checkpoint, SAC) is usually activated to delay the silk division to repair the abnormality. However, some cells "escape" the surveillance process by dividing and producing non-rectal progeny cells (aneuploidy), causing genome instability and promoting cell transformation and tumor progression. The timely detection and removal of these abnormal cells is essential to maintain the stability of the cell genome and tissue stability.
October 27, 2020, a team of Sun Qiang researchers from the Military
medical research institute, Professor Wang Xiaoning of the PLA General Hospital and Professor Huang Hongyan of the Capital Medical University published an article entitled "p53-dependent Out of Aneuploid Mitotic Offspring by Entosis" in the old journal Cell Death and Generation.
The study first reported a completely new cell-based silk division monitoring mechanism, in which non-whole-body cells can form cell-in-cell structures by drilling into adjacent cells and activating the p53 signaling path, inducing the death of a non-apoptotic cell, the entosis, the lysosome pathogenic death of cells in another cell. is selected to clear.
This mechanism expounds the physiological function of entosis, discovers the new mechanism of abnormal cell removal outside the cell cycle regulation, and reveals the new path of p53 gene to maintain the stabilising state of the skin at the cell level and inhibit the tumor, on the one hand, enriches the connotation of the existing monitoring mechanism of silk division and proves once again the physiological significance of cell-in-cell. Importantly, the findings also present a new challenge to the definition of the immune system, with traditional immunological concepts suggesting that cells that perform immune functions are primarily cells developed by bone marrow (lymphocytes, monocytes, granulocytes, etc.), suggesting that corthelial cells can also perform immune-like functions to achieve autostabilized.
value of the cell-in-cell death is found and expressed by Chinese scholar Wang Xiaoning in the early 1980s, has been recognized in the field, has been greatly reported by The Scientist. Over the past decade, the Chinese team has also uncovered and named two important cell-drilling phenomena in the field, Emperitosis (withering, one of only two pathways to internal death found so far) and in-cell infection (the virus's non-perceptive cell infection pathway), with a clear lead. This year also covered the first negative regulatory entotic cell-in-cell structure formation adhesive protein family molecule, PCDH7, in Front Cell Dev Biol magazine; The center, the largest sample size cell-in-cell type analysis and research, found that tumor cell internalized immune cell formation of heterogeneous cell formation cell-in-cell structure is the human pancreatic catheter cancer adverse prognostic relevant independent predictors, especially for young female patients with the strongest predictive effect, far stronger than the traditional histological classification and TNM phase 5, this discovery is another important contribution to the field.
nearly a decade has become a new hot spot, China's work has increasingly attracted the attention of international counterparts, I hope also caused further attention from domestic counterparts, to maintain China's leading position in this field.
The first author of the thesis is Liang Jianqing
(currently a doctoral student at Fudan University), Niu Zuxuan, an assistant researcher at the Military
Military Medical Research Institute, Zhang Bo, a doctoral student at Beijing Century Temple Hospital of Capital Medical University, and Yu Xiaochen, a master's student at the Military medical research institute of the Military
Institute of Military Medicine. Sun
, a researcher at the Military Medical Research Institute, Professor Wang Xiaoning of the PLA General Hospital, and Huang Hongyan, a professor at Beijing Century Temple Hospital of Capital Medical University, are co-authors of the paper.Researchers used cell dynamic imaging to observe in the human unconstructed endocyst MCF-10A that some cells have a short-term division block during silk division, followed by escape block successful division, while the resulting child cells will drill into adjacent cells, forming cell-in-cell structure, and then die.Further studies show that the extension of the M-period caused by silk division block, on the one hand, increases the rhoA activity in the cell, on the other hand leads to the accumulation of DNA damage, activates the downstream p53 signaling path, promotes the polarization distribution of RhoA activity in the cell by raising the small G protein RND3, and promotes the internalization of cells to form cell-in-cell structure. Further analysis of the number of internalized cell chromosomes using dynamic microscopy (time lapse microscopy) in combination with fluorescent in-place hybridization (FISH) technology showed that internalized cells were non-wholeied child cells, inhibiting the formation of a mediated cell heterosis (Entosis) in cell structures leading to a significant accumulation of non-integrated cells. (Source: Science.com)relevant paper information: h1 Musacchio, A., The Molecular Biology of Spindle Assembly Checkpoint Signaling Dynamics. Curr Biol 25, R1002-18 (2015)
【2】Liang, J., et al., p53-dependent elimination of aneuploid mitotic offspring by entosis. Cell Death Differ (2020)
【3】Wang, C., et al., PCDH7 Inhibits the Formation of Homotypic Cell-in-Cell Structure. Front Cell Dev Biol 8, 1-12 (2020)
【4】Wang, M., et al., Mechanical Ring Interfaces between Adherens Junction and Contractile Actomyosin to Coordinate Entotic Cell-in-Cell Formation. Cell Rep 32, 108071 (2020)
【5】Huang, H., et al., Identification and validation of heterotypic cell-in-cell structure as an adverse prognostic predictor for young patients of resectable pancreatic ductal adenocarcinoma. Signal Transduct Target Ther 5, 246-248 (2020)