TY - JOUR
T1 - A novel signaling network as a critical rheostat for the biology and maintenance of the normal stem cell and the cancer-initiating cell
AU - Ito, Keisuke
AU - Bernardi, Rosa
AU - Pandolfi, Pier Paolo
N1 - Funding Information:
We thank A Morotti, S Matsuoka, Y Ikeda, J Rosenblatt, DE Avigan, and J Teruya-Feldstein and all members of the Pandolfi laboratory for help, valuable comments and critical discussion KI was supported by a JSPS postdoctoral fellowship for research abroad. RB has been supported by a K01 NIH grant and is now supported by an Armenise/Harvard career development grant. This work was supported by NIH grants to PPP.
PY - 2009/2
Y1 - 2009/2
N2 - Recent advances from our own group and others have defined a novel PML/PTEN/Akt/mTOR/FoxO signaling network, and highlighted its critical importance in oncogenesis as well as in the functional regulation of normal stem cell and cancer-initiating cell (CIC) biology. These findings are of great importance in cancer therapy in view of the fact that this network is amenable to pharmacological modulation at multiple levels. The integrated analysis of these data allows us to propose a new provocative working model whereby the aberrant superactivation of Akt/mTOR signaling elicits built-in cellular fail-safe mechanisms that could be effectively utilized for cancer treatment to extinguish the CICs pool. In this review, we will discuss these recent findings, this working model, and their therapeutic implications.
AB - Recent advances from our own group and others have defined a novel PML/PTEN/Akt/mTOR/FoxO signaling network, and highlighted its critical importance in oncogenesis as well as in the functional regulation of normal stem cell and cancer-initiating cell (CIC) biology. These findings are of great importance in cancer therapy in view of the fact that this network is amenable to pharmacological modulation at multiple levels. The integrated analysis of these data allows us to propose a new provocative working model whereby the aberrant superactivation of Akt/mTOR signaling elicits built-in cellular fail-safe mechanisms that could be effectively utilized for cancer treatment to extinguish the CICs pool. In this review, we will discuss these recent findings, this working model, and their therapeutic implications.
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U2 - 10.1016/j.gde.2009.01.004
DO - 10.1016/j.gde.2009.01.004
M3 - Review article
C2 - 19216069
AN - SCOPUS:61349187121
SN - 0959-437X
VL - 19
SP - 51
EP - 59
JO - Current Opinion in Genetics and Development
JF - Current Opinion in Genetics and Development
IS - 1
ER -
