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

作者：Cano Carla E; Sandi Maria Jose; Hamidi Tewfik; Calvo Ezequiel L; Turrini Olivier; Bartholin Laurent; Loncle Celine; Secq Veronique; Garcia Stephane; Lomberk Gwen; Kroemer Guido; Urrutia Raul; Iovanna Juan L^*

来源：EMBO Molecular Medicine, 2012, 4(9): 964-979.

DOI：10.1002/emmm.201201255

• cell cannibalism
• metastasis
• Nupr1
• pancreatic cancer
• TGF ss

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 beta. 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.

• 出版日期2012-9