LKB1/AMPK/mTOR signaling pathway in hematological malignancies: From metabolism to cancer cell biology

Cell Cycle

Volumn 10, Issue 13, 2011, Pages 2115-2120

  Green, Alexa S ^a,b   Chapuis, Nicolas ^a,c   Lacombe, Catherine ^a,c   Mayeux, Patrick ^a   Bouscary, Didier ^a,c   Tamburini, Jerome ^a,c  

^a INSTITUT COCHIN   (France)

^b ROUEN UNIVERSITY HOSPITAL   (France)

^c Centre Hospitalo Universitaire de Rouen ^*  (France)

Author keywords

A 769662; AICAR; ALL; AML; CLL; LKB1 AMPK; Metformin; mTORC1

Indexed keywords

5 AMINO 4 IMIDAZOLECARBOXAMIDE RIBOSIDE; 6,7 DIHYDRO 4 HYDROXY 3 (2' HYDROXY 1,1' BIPHENYL 4 YL) 6 OXOTHIENO[2,3 B]PYRIDINE 5 CARBONITRILE; BORTEZOMIB; ELONGATION FACTOR 2 KINASE; GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; IMATINIB; INITIATION FACTOR 4E; LENALIDOMIDE; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; METFORMIN; METHOTREXATE; PHENFORMIN; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE LKB1; RAPAMYCIN;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER CELL; CANCER CHEMOTHERAPY; CELL CYCLE ARREST; CELL CYCLE G1 PHASE; CELL PROLIFERATION; CELL SURVIVAL; CELLULAR STRESS SIGNAL; CHOLESTEROL SYNTHESIS; CHRONIC LYMPHATIC LEUKEMIA; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL (TOPIC); COMPETITIVE INHIBITION; DRUG DOSE ESCALATION; FATTY ACID OXIDATION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; LIPOGENESIS; MANTLE CELL LYMPHOMA; METABOLISM; MOLECULAR BIOLOGY; MULTIPLE MYELOMA; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PROSTATE CANCER; PROTEIN CONFORMATION; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; SOMATIC MUTATION; SPLENIC MARGINAL ZONE LYMPHOMA;

EID: 79959998541     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.10.13.16244     Document Type: Review

References (33)

1. Scholl C, Gilliland DG, Frohling S. Deregulation of signaling pathways in acute myeloid leukemia. Semin Oncol 2008; 35:336-45.
2. Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: Metabolism and growth control in tumor suppression. Nature Rev 2009; 9:563-75.
3. Hezel AF, Bardeesy N. LKB1; linking cell structure and tumor suppression. Oncogene 2008; 27:6908-19.
4. Green AS, Chapuis N, Trovati Maciel T, Willems L, Lambert M, Arnoult C, et al. The LKB1/AMPK signaling pathway has tumor suppressor activity in acute myeloid leukemia through the repression of mTOR-dependent oncogenic mRNA translation. Blood 2010; 116:4262-73.
5. Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 2007; 8:774-85. (Pubitemid 47462132)
6. Tiainen M, Vaahtomeri K, Ylikorkala A, Makela TP. Growth arrest by the LKB1 tumor suppressor: induction of p21(WAF1/CIP1). Hum Mol Genet 2002; 11:1497-504. (Pubitemid 34679250)
7. Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, et al. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 2005; 18:283-93. (Pubitemid 41350534)
8. Chapuis N, Tamburini J, Green AS, Willems L, Bardet V, Park S, et al. Perspectives on inhibiting mTOR as a future treatment strategy for hematological malignancies. Leukemia 2010; 24:1686-99.
9. Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg MA, Hall A, et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 2004; 6:1122-8. (Pubitemid 39468014)
10. Guertin DA, Stevens DM, Saitoh M, Kinkel S, Crosby K, Sheen JH, et al. mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice. Cancer Cell 2009; 15:148-59.
11. Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003; 115:577-90. (Pubitemid 37506046)
12. Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 2008; 30:214-26. (Pubitemid 351626684)
13. Hardie DG. The AMP-activated protein kinase pathway - new players upstream and downstream. J Cell Sci 2004; 117:5479-87. (Pubitemid 40012195)
14. Memmott RM, Dennis PA. LKB1 and mammalian target of rapamycin as predictive factors for the anticancer efficacy of metformin. J Clin Oncol 2009; 27:226.
15. Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Sonenberg N. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res 2007; 67:10804-12. (Pubitemid 350145909)
16. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. Bmj 2005; 330:1304-5. (Pubitemid 40813563)
17. Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, et al. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 2009; 27:3297-302.
18. Robert G, Ben Sahra I, Puissant A, Colosetti P, Belhacene N, Gounon P, et al. Acadesine kills chronic myelogenous leukemia (CML) cells through PKC-dependent induction of autophagic cell death. PloS One 2009; 4:7889.
19. Puissant A, Robert G, Fenouille N, Luciano F, Cassuto JP, Raynaud S, et al. Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation. Cancer Res 70:1042-52.
20. Sengupta TK, Leclerc GM, Hsieh-Kinser TT, Leclerc GJ, Singh I, Barredo JC. Cytotoxic effect of 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) on childhood acute lymphoblastic leukemia (ALL) cells: Implication for targeted therapy. Mol Cancer 2007; 6:46.
21. Leclerc GM, Leclerc GJ, Fu G, Barredo JC. AMPK-induced activation of Akt by AICAR is mediated by IGF-1R dependent and independent mechanisms in acute lymphoblastic leukemia. J Mol Signal 2010; 5:15.
22. Kuznetsov JN, Leclerc GJ, Leclerc GM, Barredo JC. AMPK and Akt determine apoptotic cell death following perturbations of one-carbon metabolism by regulating ER stress in acute lymphoblastic leukemia. Mol Cancer Ther 2011; 10:437-47.
23. Campas C, Lopez JM, Santidrian AF, Barragan M, Bellosillo B, Colomer D, et al. Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes. Blood 2003; 101:3674-80. (Pubitemid 36857958)
24. Santidrian AF, Gonzalez-Girones DM, Iglesias-Serret D, Coll-Mulet L, Cosialls AM, de Frias M, et al. AICAR induces apoptosis independently of AMPK and p53 through upregulation of the BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia cells. Blood 2010; 116:3023-32.
25. Campas C, Santidrian AF, Domingo A, Gil J. Acadesine induces apoptosis in B cells from mantle cell lymphoma and splenic marginal zone lymphoma. Leukemia 2005; 19:292-4. (Pubitemid 40220598)
26. Drakos E, Atsaves V, Li J, Leventaki V, Andreeff M, Medeiros LJ, et al. Stabilization and activation of p53 downregulates mTOR signaling through AMPK in mantle cell lymphoma. Leukemia 2009; 23:784-90.
27. Baumann P, Mandl-Weber S, Emmerich B, Straka C, Schmidmaier R. Activation of adenosine monophosphate activated protein kinase inhibits growth of multiple myeloma cells. Exp Cell Res 2007; 313:3592-603. (Pubitemid 47404540)
28. Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, et al. The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene 2008; 27:3576-86.
29. Buzzai M, Jones RG, Amaravadi RK, Lum JJ, DeBerardinis RJ, Zhao F, et al. Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res 2007; 67:6745-52. (Pubitemid 47105521)
30. Mamane Y, Petroulakis E, LeBacquer O, Sonenberg N. mTOR, translation initiation and cancer. Oncogene 2006; 25:6416-22. (Pubitemid 44582285)
31. Brusselmans K, De Schrijver E, Verhoeven G, Swinnen JV. RNA interference-mediated silencing of the acetyl-CoA-carboxylase-alpha gene induces growth inhibition and apoptosis of prostate cancer cells. Cancer Res 2005; 65:6719-25. (Pubitemid 41060709)
32. Chajes V, Cambot M, Moreau K, Lenoir GM, Joulin V. Acetyl-CoA carboxylase alpha is essential to breast cancer cell survival. Cancer Res 2006; 66:5287-94. (Pubitemid 43844953)
33. Gan B, Hu J, Jiang S, Liu Y, Sahin E, Zhuang L, et al. Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells. Nature 2010; 468:701-4.