C Gong,
C Bauvy,
G Tonelli,
W Yue,
C Delome´ nie,
V Nicolas,
Y Zhu,
V Domergue,
V Marin-Esteban,
H Tharinger, L Delbos,
H Gary-Gouy,
A-P Morel,
S Ghavami,
E Song,
P Codogno,
M Mehrpour
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ABSTRACT: Malignant breast tissue contains a rare population of multi-potent cells with the capacity to self-renew; these cells are known as
cancer stem-like cells (CSCs) or tumor-initiating cells. Primitive mammary CSCs/progenitor cells can be propagated in culture as
floating spherical colonies termed ‘mammospheres’. We show here that the expression of the autophagy protein Beclin 1 is higher
in mammospheres established from human breast cancers or breast cancer cell lines (MCF-7 and BT474) than in the parental
adherent cells. As a result, autophagic flux is more robust in mammospheres. We observed that basal and starvation-induced
autophagy flux is also higher in aldehyde dehydrogenase 1-positive (ALDH1þ) population derived from mammospheres than in
the bulk population. Beclin 1 is critical for CSC maintenance and tumor development in nude mice, whereas its expression limits the
development of tumors not enriched with breast CSCs/progenitor cells. We found that decreased survival in autophagy-deficient
cells (MCF-7 Atg7 knockdown cells) during detachment does not contribute to an ultimate deficiency in mammosphere formation.
This study demonstrates that a prosurvival autophagic pathway is critical for CSC maintenance, and that Beclin 1 plays a dual role in
tumor development.
Oncogene 01/2012; · 6.37 Impact Factor
