Homotypic cell cannibalism, a cell-death process regulated by the nuclear protein 1, opposes to metastasis in pancreatic cancer

Carla E. Cano, María José Sandí, Tewfik Hamidi, Ezequiel L. Calvo, Olivier Turrini, Laurent Bartholin, Céline Loncle, Véronique Secq, Stéphane Garcia, Gwen Lomberk, Guido Kroemer, Raul Urrutia, Juan L. Iovanna

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Pancreatic adenocarcinoma (PDAC) is an extremely deadly disease for which all treatments available have failed to improve life expectancy significantly. This may be explained by the high metastatic potential of PDAC cells, which results from their dedifferentiation towards a mesenchymal phenotype. Some PDAC present cell-in-cell structures whose origin and significance are currently unknown. We show here that cell-in-cells form after homotypic cell cannibalism (HoCC). We found PDAC patients whose tumours display HoCC develop less metastasis than those without. In vitro, HoCC was promoted by inactivation of the nuclear protein 1 (Nupr1), and was enhanced by treatment with transforming growth factor β. HoCC ends with death of PDAC cells, consistent with a metastasis suppressor role for this phenomenon. Hence, our data indicates a protective role for HoCC in PDAC and identifies Nupr1 as a molecular regulator of this process.

Original languageEnglish (US)
Pages (from-to)964-979
Number of pages16
JournalEMBO Molecular Medicine
Volume4
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • Cell cannibalism
  • Metastasis
  • Nupr1
  • Pancreatic cancer
  • TGFβ

ASJC Scopus subject areas

  • Molecular Medicine

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    Cano, C. E., Sandí, M. J., Hamidi, T., Calvo, E. L., Turrini, O., Bartholin, L., Loncle, C., Secq, V., Garcia, S., Lomberk, G., Kroemer, G., Urrutia, R., & Iovanna, J. L. (2012). Homotypic cell cannibalism, a cell-death process regulated by the nuclear protein 1, opposes to metastasis in pancreatic cancer. EMBO Molecular Medicine, 4(9), 964-979. https://doi.org/10.1002/emmm.201201255