Open AccessHomotypic cell cannibalism, a cell‐death process regulated by the nuclear protein 1, opposes to metastasis in pancreatic cancer
Author(s) -
Cano Carla E.,
Sandí María José,
Hamidi Tewfik,
Calvo Ezequiel L.,
Turrini Olivier,
Bartholin Laurent,
Loncle Céline,
Secq Véronique,
Garcia Stéphane,
Lomberk Gwen,
Kroemer Guido,
Urrutia Raul,
Iovanna Juan L.
Publication year - 2012
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201201255
Subject(s) - cancer research , metastasis , cell , pancreatic cancer , cannibalism , programmed cell death , cancer cell , biology , suppressor , cancer , regulator , microbiology and biotechnology , apoptosis , genetics , gene , botany , larva
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.