Abstract
Descriptions of various processes that lead to cell-in-cell structures have been reported for decades. The exact molecular mechanism(s) of their formation and the physiological significance of cell-in-cell structures remain poorly understood. We had previously shown that an isoform of the CCAAT/enhancer-binding protein beta (C/EBPbeta) transcription factor, liver-enriched inhibitory protein (LIP), induces cell death in human breast cancer cells and stimulates autophagy. Here we describe a non-apoptotic cell death process where LIP mediates the engulfment of neighboring cells. We provide evidence of LIP-mediated engulfment via DNA profiling, fluorescent imaging and cell sorting studies, as well as ultrastructure analysis of LIP-expressing MDA-MB-468 breast cancer cells. Our work illustrates that expression of a specific transcription factor, LIP, can mediate cell engulfment.
Highlights
There has been a revival of interest in the phenomenon of live cell engulfment or cell-in-cell structures, catalyzed in part by the description of a nonapoptotic cell death process, termed entosis, by Overholtzer et al [1]
We reported a role for liverenriched inhibitory protein (LIP) in stimulating autophagy and causing cell death in breast cancer cell lines [6]
We evaluated the role of LIP overexpression in proliferation, necrosis, and LC3 protein turnover of MDA-MB-468 cells in particular
Summary
There has been a revival of interest in the phenomenon of live cell engulfment or cell-in-cell structures, catalyzed in part by the description of a nonapoptotic cell death process, termed entosis, by Overholtzer et al [1]. Humble et al were the first to introduce the term emperipolesis in the 1950’s to refer to a heterogeneous cell-in-cell phenomenon in which viable lymphocytes move into malignant cells [3]. During this process, the nucleus of the host cell is pressed to one side, and the internalized cell is housed in a large vacuole [3]. In cell cannibalism a host cell actively engulfs the target cell. For a review on different processes that lead to cell-in-cell structures please see [2]
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