La calpaine- 6 identifie et maintient la population de cellules souches des necones osseux en contrôlant les processus d'autophagie et de sénescence.

Abstract : Cancer stem cells contribute to sarcoma development, but lack of specific markers prevents their characterization and the possibility of targeting. We used the regulatory sequence of calpain-6 in reporter constructions to identify calpain-6–expressing cells. These cells were tumor-initiating cells and behaved like stem cells at the apex of the cellular hierarchy. Calpain-6 expression depended on the stem-cell transcription network that involves Oct4, Nanog, and Sox2 and was activated by hypoxia. Calpain-6 knockdown blocked tumor development and induced depletion of sarcoma stem cells. Calpain-6 was inversely associated with expression of senescence markers but was associated with a dynamic autophagy flux. Calpain-6 knockdown induced cell entry into senescence and suppressed autophagy flux. Our results reveal that calpain-6 identifies sarcoma stem-cell and plays an important role as a regulator of cancer cell fate driving a switch between autophagy and senescence. Calpain-6 may be a promising therapeutic target to eradicate sarcoma stem cells.
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Caroline Andrique. La calpaine- 6 identifie et maintient la population de cellules souches des necones osseux en contrôlant les processus d'autophagie et de sénescence.. Médecine humaine et pathologie. Université Sorbonne Paris Cité, 2017. Français. ⟨NNT : 2017USPCC306⟩. ⟨tel-02307922⟩

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