S. Manenti

  Cell cycle and cancer







Our research project at a glance


We try to identify proteins which are important for the response of leukemic cells to therapeutic drugs. We then investigate how these proteins work in these cells, and how they are regulated by the oncogenes responsible of the disease. We focus our studies on proteins which have important functions in cell cycle regulation, as well as in autophagy, a cellular process recently identified as an important pathway of resistance to several therapeutic drugs.




Our general aim is to decipher the mechanisms that link oncogenic signaling, cell cycle regulation, and autophagy. We try to understand how cell signaling pathways activated by oncogenes, in particular mutated tyrosine kinases, regulate key cell cycle actors, like the CDC25A phosphatase or the DNA damage checkpoint kinase CHK1, for instance.

We identify by different approaches new regulatory modifications of these proteins, such as new phosphorylation sites or new transcriptional and post-transcriptional mechanisms of regulation.

We also investigate how autophagy regulates signaling pathways (signalophagy) in cancer cells, more specifically in acute myeloid leukemia subtypes. We estimate in parallel how these cell cycle actors or autophagy impact the response and the resistance of these cancer cells to therapeutic agents.

We finally translate these basic research questions into the identification of potential therapeutic targets in acute myeloid leukemia.


Key words


  • Cell cycle
  • Autophagy
  • Signaling
  • Acute myeloid leukemia
  • Checkpoints
  • CDK inhibitor


Selected publications


Dozier, C; Mazzolini, L; Cenac, C; Froment, C; Burlet-Schiltz, O; Besson, A; Manenti, S

CyclinD-CDK4/6 complexes phosphorylate CDC25A and regulate its stability Journal Article

Oncogene, 36 (26), pp. 3781-3788, 2017, ISSN: 1476-5594 (Electronic) 0950-9232 (Linking).

Links | BibTeX

Jeannot, P; Nowosad, A; Perchey, R T; Callot, C; Bennana, E; Katsube, T; Mayeux, P; Guillonneau, F; Manenti, S; Besson, A

p27Kip1 promotes invadopodia turnover and invasion through the regulation of the PAK1/Cortactin pathway Journal Article

Elife, 6 , 2017, ISSN: 2050-084X (Electronic) 2050-084X (Linking).

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Joffre, C; Djavaheri-Mergny, M; Pattingre, S; Giuriato, S

[The yin and the yang of autophagy in cancer cells] Journal Article

Med Sci (Paris), 33 (3), pp. 328-334, 2017, ISSN: 1958-5381 (Electronic) 0767-0974 (Linking).

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David, L; Fernandez-Vidal, A; Bertoli, S; Grgurevic, S; Lepage, B; Deshaies, D; Prade, N; Cartel, M; Larrue, C; Sarry, J E; Delabesse, E; Cazaux, C; Didier, C; Recher, C; Manenti, S; Hoffmann, J S

CHK1 as a therapeutic target to bypass chemoresistance in AML Journal Article

Sci Signal, 9 (445), pp. ra90, 2016, ISSN: 1937-9145 (Electronic) 1945-0877 (Linking).

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Duquesnes, N; Callot, C; Jeannot, P; Daburon, V; Nakayama, K I; Manenti, S; Davy, A; Besson, A

p57(Kip2) knock-in mouse reveals CDK-independent contribution in the development of Beckwith-Wiedemann syndrome Journal Article

J Pathol, 239 (3), pp. 250-61, 2016, ISSN: 1096-9896 (Electronic) 0022-3417 (Linking).

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Larrue, C; Saland, E; Boutzen, H; Vergez, F; David, M; Joffre, C; Hospital, M A; Tamburini, J; Delabesse, E; Manenti, S; Sarry, J E; Recher, C

Proteasome inhibitors induce FLT3-ITD degradation through autophagy in AML cells Journal Article

Blood, 127 (7), pp. 882-92, 2016, ISSN: 1528-0020 (Electronic) 0006-4971 (Linking).

Links | BibTeX

Mazzolini, L; Broban, A; Froment, C; Burlet-Schiltz, O; Besson, A; Manenti, S; Dozier, C

Phosphorylation of CDC25A on SER283 in late S/G2 by CDK/cyclin complexes accelerates mitotic entry Journal Article

Cell Cycle, 15 (20), pp. 2742-52, 2016, ISSN: 1551-4005 (Electronic) 1551-4005 (Linking).

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Bertoli, S; Boutzen, H; David, L; Larrue, C; Vergez, F; Fernandez-Vidal, A; Yuan, L; Hospital, M A; Tamburini, J; Demur, C; Delabesse, E; Saland, E; Sarry, J E; Galcera, M O; Mansat-De Mas, V; Didier, C; Dozier, C; Recher, C; Manenti, S

CDC25A governs proliferation and differentiation of FLT3-ITD acute myeloid leukemia Journal Article

Oncotarget, 6 (35), pp. 38061-78, 2015, ISSN: 1949-2553 (Electronic) 1949-2553 (Linking).

Links | BibTeX

Larrue, C; Saland, E; Vergez, F; Serhan, N; Delabesse, E; Mansat-De Mas, V; Hospital, M A; Tamburini, J; Manenti, S; Sarry, J E; Recher, C

Antileukemic Activity of 2-Deoxy-d-Glucose through Inhibition of N-Linked Glycosylation in Acute Myeloid Leukemia with FLT3-ITD or c-KIT Mutations Journal Article

Mol Cancer Ther, 14 (10), pp. 2364-73, 2015, ISSN: 1538-8514 (Electronic) 1535-7163 (Linking).

Links | BibTeX