A functional link between polo-like kinase 1 and the mammalian target-of-rapamycin pathway?
Polo like kinase-1 is a key effector of cell division and its overexpression in several cancers is often linked with negative prognostic. We recently described that Plk1 is overexpressed in acute myeloid leukemia, and that its inhibition selectively reduces the proliferation of leukemic cells. Here, we report that Plk1 inhibition or depletion using pharmacological and siRNA approaches decreased the phosphorylation of two mTOR substrates in AML cells. In HCT116 cells, inducible expression of a constitutively active form of Plk1 leads to activation of mTOR, as shown by increased phosphorylation of its 4E-BP1 and RPS6 down-stream targets. In addition, cells overexpressing the active form of Plk1 were characterized by abnormal growth that could be reversed by rapamycin, a specific inhibitor of the TORC1 complex. Altogether these data suggest the existence of a molecular and functional link between the Plk1 mitotic kinase and the mTOR pathway. Given the different established functions of Plk1 and mTOR during the cell cycle, we will discuss the possible meaning of this functional relationship.
Renner
Annelies G
AG
INSERM, U563-IFR30, Centre de Physiopathologie Toulouse-Purpan, Département Oncogenèse et Signalisation dans les cellules hématopoïétiques CHU Purpan, Toulouse, France.
Créancier
Laurent
L
Dos Santos
Cédric
C
Fialin
Camille
C
Recher
Christian
C
Bailly
Christian
C
Kruczynski
Anna
A
Payrastre
Bernard
B
Manenti
Stéphane
S
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D016193:G1 Phase; D045325:HCT116 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D000097869:Polo-Like Kinase 1
D048868:Adaptor Proteins, Signal Transducing; D000903:Antibiotics, Antineoplastic; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D000097869:Polo-Like Kinase 1; C087000:EIF4EBP1 protein, human; C546842:MTOR protein, human