Competition between human cells by entosis

Qiang Sun, Tianzhi Luo, Yixin Ren, Oliver Florey, Senji Shirasawa, Takehiko Sasazuki, Douglas Robinson, Michael Overholtzer

Research output: Contribution to journalArticle

Abstract

Human carcinomas are comprised of complex mixtures of tumor cells that are known to compete indirectly for nutrients and growth factors. Whether tumor cells could also compete directly, for example by elimination of rivals, is not known. Here we show that human cells can directly compete by a mechanism of engulfment called entosis. By entosis, cells are engulfed, or cannibalized while alive, and subsequently undergo cell death. We find that the identity of engulfing ("winner") and engulfed ("loser") cells is dictated by mechanical deformability controlled by RhoA and actomyosin, where tumor cells with high deformability preferentially engulf and outcompete neighboring cells with low deformability in heterogeneous populations. We further find that activated Kras and Rac signaling impart winner status to cells by downregulating contractile myosin, allowing for the internalization of neighboring cells that eventually undergo cell death. Finally, we compute the energy landscape of cell-in-cell formation, demonstrating that a mechanical differential between winner and loser cells is required for entosis to proceed. These data define a mechanism of competition in mammalian cells that occurs in human tumors.

Original languageEnglish (US)
Pages (from-to)1299-1310
Number of pages12
JournalCell Research
Volume24
Issue number11
DOIs
StatePublished - Nov 5 2014

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Entosis
Cell-in-Cell Formation
Neoplasms
Cell Death
Actomyosin

Keywords

  • cell cannibalism
  • cell competition
  • cell-in-cell structure
  • entosis
  • Kras
  • Rho GTPase
  • tumor evolution

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Sun, Q., Luo, T., Ren, Y., Florey, O., Shirasawa, S., Sasazuki, T., ... Overholtzer, M. (2014). Competition between human cells by entosis. Cell Research, 24(11), 1299-1310. https://doi.org/10.1038/cr.2014.138

Competition between human cells by entosis. / Sun, Qiang; Luo, Tianzhi; Ren, Yixin; Florey, Oliver; Shirasawa, Senji; Sasazuki, Takehiko; Robinson, Douglas; Overholtzer, Michael.

In: Cell Research, Vol. 24, No. 11, 05.11.2014, p. 1299-1310.

Research output: Contribution to journalArticle

Sun, Q, Luo, T, Ren, Y, Florey, O, Shirasawa, S, Sasazuki, T, Robinson, D & Overholtzer, M 2014, 'Competition between human cells by entosis', Cell Research, vol. 24, no. 11, pp. 1299-1310. https://doi.org/10.1038/cr.2014.138
Sun Q, Luo T, Ren Y, Florey O, Shirasawa S, Sasazuki T et al. Competition between human cells by entosis. Cell Research. 2014 Nov 5;24(11):1299-1310. https://doi.org/10.1038/cr.2014.138
Sun, Qiang ; Luo, Tianzhi ; Ren, Yixin ; Florey, Oliver ; Shirasawa, Senji ; Sasazuki, Takehiko ; Robinson, Douglas ; Overholtzer, Michael. / Competition between human cells by entosis. In: Cell Research. 2014 ; Vol. 24, No. 11. pp. 1299-1310.
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