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Entosis is a cell-in-cell (CIC)-mediated death program. Contractile actomyosin (CA) and the adherens junction (AJ) are two core elements essential for entotic CIC formation, but the molecular structures interfacing them remain poorly understood. Here, we report the characterization of a ring-like structure interfacing between the peripheries of invading and engulfing cells. The ring-like structure is a multi-molecular complex consisting of adhesive and cytoskeletal proteins, in which the mechanical sensor vinculin is highly enriched. The vinculin-enriched structure senses mechanical force imposed on cells, as indicated by fluorescence resonance energy transfer (FRET) analysis, and is thus termed the mechanical ring (MR). The MR actively interacts with CA and the AJ to help establish and maintain polarized actomyosin that drives cell internalization. Vinculin depletion leads to compromised MR formation, CA depolarization, and subsequent CIC failure. In summary, we suggest that the vinculin-enriched MR, in addition to CA and AJ, is another core element essential for entosis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Homotypic cell-in-cell (CIC) structures forming between cancer cells were proposed to promote tumor evolution via entosis, a nonapoptotic cell death process. However, the mechanisms underlying their formation remained poorly understood. We performed a microarray analysis to identify genes associated with homotypic CIC formation. Cancer cells differing in their ability to form homotypic CIC structures were selected for the study. Association analysis identified 73 probe sets for 62 candidate genes potentially involved in CIC formation. Among them, twenty-one genes were downregulated while 41 genes were upregulated. Pathway analysis identified a gene interaction network centered on IL-8, which was upregulated in high CIC cells. Remarkably, CIC formation was significantly inhibited by IL-8 knockdown and enhanced upon recombinant IL-8 treatment, which correlated with altered cell-cell adhesion and expression of adhesive molecules such as P-cadherin and γ-catenin. Together, our work identified IL-8 as a positive regulator of homotypic CIC formation via enhancing intercellular adhesion. [BMB Reports 2018; 51(8): 412-417].

Cell cannibalism is a unique pathological phenomenon that has been observed at low frequency in a variety of human tumor samples (<0.5%), including breast cancer. Cannibalistic cells typically form cell-in-cell (CIC) structures characterized by enclosure of one cell or more by another, mediating a novel type of cell death "entosis," which was proposed as the type IV cell death. A large number of CIC structures are generally associated with malignant transformation and progression, and they are believed to be primed by and form among heterogeneous cells. However, there is currently no in vivo evidence from human tumor samples. In this case report, covering a 37-year-old female breast cancer patient, we observed considerable heterogeneity and proliferative activity (>70% Ki-67 positivity) in her breast cancer cells, accompanied by high frequency of CIC formation (~6%) and poor prognosis. We consider this a typical example of cell cannibalism, supporting a role of heterogeneity in cell-in-cell formation and malignant progression. It may serve as a pretest basis for further investigations of cell-in-cell biology and breast cancer treatment. [ABSTRACT FROM AUTHOR]