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Molecular mechanisms underlying cell-in-cell formation: core machineries and beyond
Zubiao Niu1,† , Meifang He2,† , Qiang Sun1,3,†,*
1Laboratory of Cell Engineering, Institute of Biotechnology, Beijing 100071, China
2Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
3Research Unit of Cell Death Mechanism, Chinese Academy of Medical Sciences, 2020RU009, Beijing 100071, China
These authors contributed equally to this work.
*Correspondence to:Qiang Sun ,
J Mol Cell Biol, Volume 13, Issue 5, May 2021, 329-334,

Although cell-in-cell structures (CICs), with one or more cells present inside another cell, had been identified for a century, it was not until recent years that scientists started to uncover their pivotal roles in multiple biological processes, primarily via mediating the death of internalized cells. Meanwhile, considerable progresses were made on deciphering the mechanisms underlying their formation based on different models. Entosis was one of the best investigated CIC models, where cell internalization was coordinately driven by adherens junction and contractile actomyosin, the two spatially polarized and complementary core elements that were coupled by mechanical ring, a recently identified core element. Meanwhile, an expanding group of factors were found capable of regulating CIC formation by targeting these core elements. The elucidation of the molecular machinery controlling CIC formation enables synthetic engineering of cells used for clinical and research purposes. With the growing academic and translational interests in CICs, this perspective essay attempts to make an in-time updating of the latest progress on the molecular controls of CIC formation in the hope of moving the field forward.