mTORC1 is essential for leukemia propagation but not stem cell self-renewal
Citations
2,194 citations
824 citations
Cites background from "mTORC1 is essential for leukemia pr..."
...Phosphorylation of p62 and induction of Nqo1 both decreased upon As(III) exposure in MEFs lacking Raptor (Hoshii et al., 2012), a component of the mTORC1 complex (Figures S2B and S2C)....
[...]
262 citations
255 citations
Cites background from "mTORC1 is essential for leukemia pr..."
...Conversely, the deletion of the MTORC1 component RAPTOR, therefore theoretically causing an increase in autophagy, results in a decrease of this myeloid population.(91) However, it remains to be shown definitively that loss or gain of autophagy contributes to this phenotype, as MTOR inhibition signals for many other important cellular functions such as inhibition of protein translation, mitochondrial biogenesis, cell growth, motility and proliferation....
[...]
238 citations
Cites background from "mTORC1 is essential for leukemia pr..."
...Recently, it was shown in a raptor deficiency mouse model thatmTORC1 inactivation induces apoptosis in differentiated leukemic cells and maintains immature leukemic cells with leukemia initiation potential in a dormant state, underlying the critical role of mTORC1 in leukemia.(4) In vitro, in primary AML cells, mTORC1 inhibition with rapamycin has cytostatic effects but does not induce apoptosis,(2-5) mainly because it does not inhibit 4E-BP1 phosphorylation on ser65....
[...]
References
711 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...Although S6 and eEF2K are substrates of p70S6K, it was also reported that p90 RSK can phosphorylate these proteins (28, 30)....
[...]
695 citations
685 citations
667 citations
666 citations
"mTORC1 is essential for leukemia pr..." refers background in this paper
...Because the proliferation is restored by 4E-BP1/2 deficiency, 4E-BPs are thought to be key regulators of cell proliferation when mTORC1 activity is downregulated (45)....
[...]
...Previous studies demonstrated that mTORC1 activity plays critical roles in cell proliferation in embryonic fibroblasts and cell lines (45, 46)....
[...]