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Metabolic changes promote rejection of oncogenic cells

Nature Cell Biology volume 19, pages 414–415 (2017)Cite this article

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Dysfunctional cells are eliminated from epithelial monolayers by a process known as cell extrusion to maintain tissue homeostasis. Normal epithelial cells are now shown to induce the extrusion of oncogene-transformed cells by inducing metabolic changes in the oncogene-expressing cells through PDK4-mediated inhibition of PDH and mitochondrial metabolism.

Maintenance of epithelial tissues involves the continuous turnover of old and defective cells. One mechanism by which this occurs is through the extrusion of unwanted cells from epithelial cell layers. In this process, unwanted cells are forced to detach from the basement membrane where they undergo a form of apoptosis known as anoikis due to the loss of attachment to extracellular matrix (ECM) proteins. Cellular extrusion can be induced as a result of multiple stimuli, including cell crowding associated with relatively rapidly proliferating epithelial cells such as those found in the lining of the intestines, or conditions that cause cell damage1,2. Extrusion is an active process mediated by the surrounding normal cells and allows the maintenance of proper epithelial function while the unwanted cells are eliminated. This homeostatic cell extrusion mechanism has been proposed to be involved in multiple pathologic processes that involve loss of critical barrier functions and pathogen defences1.

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Figure 1: The reciprocal relationship between ECM interaction and PDK4-induced metabolic changes, and the potential fates of apically extruded transformed cells.

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  1. Jonathan L. Coloff and Joan S. Brugge are in the Department of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, Massachussetts, USA,

    Jonathan L. Coloff & Joan S. Brugge

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  1. Jonathan L. Coloff
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  2. Joan S. Brugge
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Correspondence to Joan S. Brugge.

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Coloff, J., Brugge, J. Metabolic changes promote rejection of oncogenic cells. Nat Cell Biol 19, 414–415 (2017). https://doi.org/10.1038/ncb3521

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