A novel signaling network as a critical rheostat for the biology and maintenance of the normal stem cell and the cancer-initiating cell.
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.
Ito
Keisuke
K
Department of Medicine, Beth Israel Deaconess Cancer Center, Harvard Medical School, Boston, MA 02215, USA.
Bernardi
Rosa
R
Pandolfi
Pier Paolo
PP
D000818:Animals; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins / Q000502:physiology
D051858:Forkhead Transcription Factors; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase