The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis

Silvia Crespo* , Marcus Kind* , Alexandre Arcaro

Journal of Cancer Metastasis and Treatment ›› 2016, Vol. 2 : 80 -9.

PDF
Journal of Cancer Metastasis and Treatment ›› 2016, Vol. 2:80 -9. DOI: 10.20517/2394-4722.2015.72
Original Article
review-article

The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis

Author information +
History +
PDF

Abstract

The PI3K/AKT/mTOR (PAM) pathway is involved in a variety of cellular functions and often contributes to oncogenesis and cancer progression. It has been recognized that this pathway is frequently activated in the most common central nervous system cancers of adults and children, malignant gliomas and medulloblastomas (MB). In these tumors, the PAM network controls key functions necessary for cell invasion and metastasis, such as cell motility. This review summarizes the current knowledge about the role of PAM signaling in cell invasion and metastasis in gliomas and MB. Current approaches to inhibit cell invasion and metastasis by targeting the PAM pathway will also be discussed.

Keywords

PI3K/AKT/mTOR pathway / glioblastoma / medulloblastoma / metastasis

Cite this article

Download citation ▾
Silvia Crespo*, Marcus Kind*, Alexandre Arcaro. The role of the PI3K/AKT/mTOR pathway in brain tumor metastasis. Journal of Cancer Metastasis and Treatment, 2016, 2: 80-9 DOI:10.20517/2394-4722.2015.72

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Louis DN,Wiestler OD,Burger PC,Scheithauer BW.The 2007 WHO classification of tumours of the central nervous system..Acta Neuropathol2007;114:97-109 PMCID:PMC1929165

[2]

Johnson DR.Glioblastoma survival in the United States before and during the temozolomide era..J Neurooncol2012;107:359-64

[3]

Grimmer MR.Childhood tumors of the nervous system as disorders of normal development..Curr Opin Pediatr2006;18:634-8

[4]

Gajjar AJ.Medulloblastoma-translating discoveries from the bench to the bedside..Nat Rev Clin Oncol2014;11:714-22

[5]

Cancer Genome Atlas Research Network.Comprehensive genomic characterization defines human glioblastoma genes and core pathways..Nature2008;455:1061-8 PMCID:PMC2671642

[6]

Northcott PA,Peacock J,Morrissy AS,Stütz AM,Reimand J,Beroukhim R,Marshall CR,Mack S,Yao Y,Luu B,Cavalli FM,Remke M,Chiu RY,Chuah E,Hoad GR,Li Y,Mungall KL,Qian JQ,Thiessen NT,Birol I,Mungall AJ,Kawauchi D,Kool M,Witt H,Kenney AM,Dirks P,Grajkowska WA,Haberler CC,Reynaud SS,Pernet-Fattet SS,Kim SK,Scheurlen W,Fèvre-Montange M,Pollack IF,Muraszko KM,Di Rocco C,Michiels EM,French PJ,Olson JM,Zitterbart K,Thompson RC,Lach B,Bigner DD,Albrecht S,Lindsey JC,Gupta N,Bognár L,Van Meter TE,Tominaga T,Leonard JR,Liau LM,Fouladi M,Cinalli G,Hauser P,Iolascon A,Carlotti CG,Ra YS,Zollo M,Chan JA,Sorensen PH,Pomeroy SL,Bader GD,Hawkins CE,Scherer SW,Malkin D,Jones SJ,Pfister SM,Taylor MD.Subgroup-specific structural variation across 1,000 medulloblastoma genomes..Nature2012;488:49-56 PMCID:PMC3683624

[7]

Engelman JA,Cantley LC.The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism..Nat Rev Genet2006;7:606-19

[8]

Cantley LC.The phosphoinositide 3-kinase pathway..Science2002;296:1655-7

[9]

Vanhaesebroeck B,Panayotou G.Phosphoinositide 3-kinases: a conserved family of signal transducers..Trends Biochem Sci1997;22:267-72

[10]

Lemmon MA.Membrane recognition by phospholipid-binding domains..Nat Rev Mol Cell Biol2008;9:99-111

[11]

Hatanpaa KJ,Zhao D.Epidermal growth factor receptor in glioma: signal transduction, neuropathology, imaging, and radioresistance..Neoplasia2010;12:675-84 PMCID:PMC2933688

[12]

Quayle SN,Cheung LW,Wiedemeyer R,Huang-Hobbs E,Wilson RK,Mills GB,Chin L.Somatic mutations of PIK3R1 promote gliomagenesis..PloS one2012;7:e49466

[13]

Castellino RC,Schniederjan M,Becher O,Macdonald TJ,Durden DL.Heterozygosity for Pten promotes tumorigenesis in a mouse model of medulloblastoma..PloS one2010;5:e10849

[14]

Zhao D,Wander SA,Zhou W,Ince T,Guo W,Theodorescu D.Cytoplasmic p27 promotes epithelial-mesenchymal transition and tumor metastasis via STAT3-mediated Twist1 upregulation..Oncogene2015;34:5447-59 PMCID:PMC4537852

[15]

Yoshioka K,Cui H,Takuwa N,Du W,Asanuma K,Aki S,Biswas K,Ueno M,Schwartz RJ,Sasaki T,Asano M,Takakura N.Endothelial PI3K-C2alpha, a class II PI3K, has an essential role in angiogenesis and vascular barrier function..Nat Med2012;18:1560-9

[16]

Holand K,Hagel C,Treszl A,Cwiek P,Leni Z,Styp-Rekowska B,von Bueren AO,Arcaro A.Targeting class IA PI3K isoforms selectively impairs cell growth, survival, and migration in glioblastoma..PloS one2014;9:e94132

[17]

Huse JT.Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma..Nat Rev Cancer2010;10:319-31

[18]

Dimitrova V.Targeting the PI3K/AKT/mTOR signaling pathway in medulloblastoma..Curr Mol Med2015;15:82-93

[19]

Nagy JA.Heterogeneity of the tumor vasculature: the need for new tumor blood vessel type-specific targets..Clin Exp Metastasis2012;29:657-62 PMCID:PMC3484269

[20]

Schmid MC.Myeloid cell trafficking and tumor angiogenesis..Cancer Lett2007;250:1-8 PMCID:PMC3167210

[21]

Zhong H,Feldser D,Hanrahan C,Simons JW.Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics..Cancer Res2000;60:1541-5

[22]

Xia C,Cao Z,Jiang BH.Regulation of angiogenesis and tumor growth by p110 alpha and AKT1 via VEGF expression..J Cell Physiol2006;209:56-66

[23]

Brazil DP,Hemmings BA.PKB binding proteins. Getting in on the Akt..Cell2002;111:293-303

[24]

Galetic I,Meier R,Park J.Mechanism of protein kinase B activation by insulin/insulin-like growth factor-1 revealed by specific inhibitors of phosphoinositide 3-kinase-significance for diabetes and cancer..Pharmacol Ther1999;82:409-25

[25]

Hu L,Jaffe RB.Phosphatidylinositol 3-kinase mediates angiogenesis and vascular permeability associated with ovarian carcinoma..Clin Cancer Res2005;11:8208-12

[26]

Schmid MC,Dippold HC,Foubert P,Acevedo LM,Song X,Blair SL,Cheresh DA,Field SJ.Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kgamma, a single convergent point promoting tumor inflammation and progression..Cancer cell2011;19:715-27 PMCID:PMC3144144

[27]

Semenza GL.HIF-1 and tumor progression: pathophysiology and therapeutics..Trends Mol Med2002;8:S62-7

[28]

Su JD,Donner DB.PTEN and phosphatidylinositol 3'-kinase inhibitors up-regulate p53 and block tumor-induced angiogenesis: evidence for an effect on the tumor and endothelial compartment..Cancer Res2003;63:3585-92

[29]

Garlich JR,Dey N,Peng X,Murali R,Mills GB,Shu HK,Durden DL.A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity..Cancer Res2008;68:206-15

[30]

Koul D,Kim YW,Lu Y,Ronen SM,Powis G.Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma..Neuro Oncol2010;12:559-69 PMCID:PMC2940638

[31]

Pitz MW,MacNeil MV,Easaw JC,Eisenstat DD,Salim M,Squire J,Kamel-Reid S,Tu D,Hausman DF.Phase II study of PX-866 in recurrent glioblastoma..Neuro Oncol2015;17:1270-4

[32]

Sharma PS,Tyagi T.VEGF/VEGFR pathway inhibitors as anti-angiogenic agents: present and future..Curr Cancer Drug Targets2011;11:624-53

[33]

Reardon DA,Peters KB,Gururangan S,McLendon RE,Jones LW,Friedman AH,Bigner DD.A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma..J Natl Compr Canc Netw2011;9:414-27 PMCID:PMC3399727

[34]

Kuczynski EA,Coomber BL.VEGFR2 expression and TGF-beta signaling in initial and recurrent high-grade human glioma..Oncology2011;81:126-34

[35]

Chinot OL,Moore N,Das A,Modrusan Z.AVAglio: Phase 3 trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma multiforme..Adv Ther2011;28:334-40

[36]

Van Meir EG,Norden AD,Wen PY.Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma..CA Cancer J Clin2010;60:166-93 PMCID:PMC2888474

[37]

Hardee ME.Mechanisms of glioma-associated neovascularization..Am J Pathol2012;181:1126-41 PMCID:PMC3463636

[38]

Takano S,Ohneda O.Molecular therapeutic targets for glioma angiogenesis..J Oncol2010;2010:351908 PMCID:PMC2857608

[39]

di Tomaso E,Kamoun WS,Auluck PK,Andronesi OC,Wen PY,Hedley-Whyte ET,Batchelor TT.Glioblastoma recurrence after cediranib therapy in patients: lack of "rebound" revascularization as mode of escape..Cancer Res2011;71:19-28 PMCID:PMC3074948

[40]

Gerstner ER,Wen PY,Batchelor TT.Infiltrative patterns of glioblastoma spread detected via diffusion MRI after treatment with cediranib..Neuro Oncol2010;12:466-72

[41]

Navis AC,Wesseling P,Hendriks W,van der Laak JA,Leenders WP.Effects of dual targeting of tumor cells and stroma in human glioblastoma xenografts with a tyrosine kinase inhibitor against c-MET and VEGFR2..PloS one2013;8:e58262

[42]

Bridges E.Vascular-promoting therapy reduced tumor growth and progression by improving chemotherapy efficacy..Cancer cell2015;27:7-9

[43]

Donnem T,Ferguson M,Snell C,Gatter KC.Vessel co-option in primary human tumors and metastases: an obstacle to effective anti-angiogenic treatment?.Cancer Med2013;2:427-36

[44]

Qian CN.Hijacking the vasculature in ccRCC-co-option, remodelling and angiogenesis..Nat Rev Urol2013;10:300-4

[45]

Nguyen TM,Kelekar A.Kringle 5 of human plasminogen, an angiogenesis inhibitor, induces both autophagy and apoptotic death in endothelial cells..Blood2007;109:4793-802

[46]

Ramakrishnan S,Subramanian IV.Autophagy and angiogenesis inhibition..Autophagy2007;3:512-5

[47]

Du J,Guan T,Kaul S,Shi Y.Role of autophagy in angiogenesis in aortic endothelial cells..Am J Physiol Cell Physiol2012;302:C383-91

[48]

Shen W,Chen H,Zhu D,Liu J.Oxidative stress mediates chemerin-induced autophagy in endothelial cells..Free Radic Biol Med2013;55:73-82

[49]

Brech A,Lothe RA.Autophagy in tumour suppression and promotion..Mol Oncol2009;3:366-75 PMCID:PMC5527946

[50]

Manning BD.AKT/PKB signaling: navigating downstream..Cell2007;129:1261-74 PMCID:PMC2756685

[51]

Bhandarkar SS.Curcumin as an inhibitor of angiogenesis..Adv Exp Med Biol2007;595:185-95

[52]

Igura K,Kuroda Y.Resveratrol and quercetin inhibit angiogenesis in vitro..Cancer Lett2001;171:11-6

[53]

Lau DH,Young LJ,Cheung AT.Paclitaxel (Taxol): an inhibitor of angiogenesis in a highly vascularized transgenic breast cancer..Cancer Biother Radiopharm1999;14:31-6

[54]

Pirtoli L,Tini P,Oliveri G,Mourmouras V,Miracco C.The prognostic role of Beclin 1 protein expression in high-grade gliomas..Autophagy2009;5:930-6

[55]

Weihua Z,Huang WC,Chiu CH,Hung MC.Survival of cancer cells is maintained by EGFR independent of its kinase activity..Cancer cell2008;13:385-93 PMCID:PMC2413063

[56]

Huang X,Chen L,Lu YC.Reduced expression of LC3B-II and Beclin 1 in glioblastoma multiforme indicates a down-regulated autophagic capacity that relates to the progression of astrocytic tumors..J Clin Neurosci2010;17:1515-9

[57]

Micalizzi DS,Ford HL.Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression..J Mammary Gland Biol Neoplasia2010;15:117-34 PMCID:PMC2886089

[58]

Kalluri R.Epithelial-mesenchymal transition and its implications for fibrosis..J Clin Invest2003;112:1776-84 PMCID:PMC297008

[59]

Kalluri R.The basics of epithelial-mesenchymal transition..J Clin Invest2009;119:1420-8 PMCID:PMC2689101

[60]

Boutet A,Maxwell PH.Reactivation of Snail genes in renal fibrosis and carcinomas: a process of reversed embryogenesis?.Cell cycle2007;6:638-42

[61]

Grille SJ,Upson J,van Roy F,Donowitz M,Larue L.The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines..Cancer Res2003;63:2172-8

[62]

Vega S,Ocana OH,Fabregat I.Snail blocks the cell cycle and confers resistance to cell death..Genes Dev2004;18:1131-43 PMCID:PMC415638

[63]

Yang J,Donaher JL,Itzykson RA,Savagner P,Richardson A.Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis..Cell2004;117:927-39

[64]

Cheng GZ,Wang LH.Regulation of cancer cell survival, migration, and invasion by Twist: AKT2 comes to interplay..Cancer Res2008;68:957-60

[65]

Xue G,Lan Q,Dirnhofer S,Rüegg C.Akt/PKB-mediated phosphorylation of Twist1 promotes tumor metastasis via mediating cross-talk between PI3K/Akt and TGF-beta signaling axes..Cancer Discov2012;2:248-59

[66]

Wallin JJ,Edgar KA,Francis R,Haverty PM,Arena S,Griffin S,Grimshaw KM,Torrance C,Friedman LS.Active PI3K pathway causes an invasive phenotype which can be reversed or promoted by blocking the pathway at divergent nodes..PloS one2012;7:e36402

[67]

Wik E,Krakstad C,Birkeland E,Mjos S,Mannelqvist M,Oyan AM,Akslen LA.Lack of estrogen receptor-alpha is associated with epithelial-mesenchymal transition and PI3K alterations in endometrial carcinoma..Clin Cancer Res2013;19:1094-105

[68]

Elias MC,Silber JR,Deng M,Manning TC,Glackin CA,Rostomily RC.TWIST is expressed in human gliomas and promotes invasion..Neoplasia2005;7:824-37 PMCID:PMC1501937

[69]

Dunn GP,Ikeda H,Schreiber RD.Cancer immunoediting: from immunosurveillance to tumor escape..Nat Immunol2002;3:991-8

[70]

Shahideh M,Munoz DG.Systematic review of primary intracranial glioblastoma multiforme with symptomatic spinal metastases, with two illustrative patients..J Clin Neurosci2012;19:1080-6

[71]

Lawton CD,Yang I,Smith ZA.Leptomeningeal spinal metastases from glioblastoma multiforme: treatment and management of an uncommon manifestation of disease..J Neurosurg Spine2012;17:438-48

[72]

Kalokhe G,Chandler JP,Rademaker A.Metastatic glioblastoma: case presentations and a review of the literature..J Neurooncol2012;107:21-7

[73]

Taylor MD,Korshunov A,Cho YJ,Eberhart CG,Rutkowski S,Ellison DW,Gilbertson RJ,Kool M.Molecular subgroups of medulloblastoma: the current consensus..Acta Neuropathol2012;123:465-72 PMCID:PMC3306779

[74]

Gajjar A,Karajannis MA,Witt H.Pediatric Brain Tumors: Innovative Genomic Information Is Transforming the Diagnostic and Clinical Landscape..J Clin Oncol2015;33:2986-98 PMCID:PMC4567701

[75]

Robinson G,Kranenburg TA,Chen X,Phoenix TN,Wei L,Chalhoub N,Huether R,Curley N,Wang J,Rusch M,Becksfort J,Ma J,Vadodaria B,Lin T,Pounds S,Zhao D,Roussel MF,Ellison DW,Bouffet E,Gururangan S,Fulton RS,Dooling DJ,Gajjar A,Wilson RK,Zhang J.Novel mutations target distinct subgroups of medulloblastoma..Nature2012;488:43-8 PMCID:PMC3412905

[76]

Blom T,Hayry V,Wartiovaara K,Nordfors K,Nupponen NN.Amplification and overexpression of KIT, PDGFRA, and VEGFR2 in medulloblastomas and primitive neuroectodermal tumors..J Neurooncol2010;97:217-24

[77]

Holand K,Arcaro A.The phosphoinositide 3-kinase signaling pathway as a therapeutic target in grade IV brain tumors..Curr Cancer Drug Targets2011;11:894-918

[78]

Hartmann C,Gehlhaar C,von Deimling A.PIK3CA mutations in glioblastoma multiforme..Acta Neuropathol2005;109:639-42

[79]

Guerreiro AS,Fischer B,Jackson SP,Grotzer MA,Arcaro A.Targeting the PI3K p110alpha isoform inhibits medulloblastoma proliferation, chemoresistance, and migration..Clin Cancer Res2008;14:6761-9

[80]

Salm F,von Bueren AO,Rehrauer H,Anderle P.The Phosphoinositide 3-Kinase p110alpha Isoform Regulates Leukemia Inhibitory Factor Receptor Expression via c-Myc and miR-125b to Promote Cell Proliferation in Medulloblastoma..PloS one2015;10:e0123958

[81]

Mueller W,Silen E,Nutt CL.Mutations of the PIK3CA gene are rare in human glioblastoma..Acta Neuropathol2005;109:654-5

[82]

Luk SK,Nurnberg B.The catalytic phosphoinositol 3-kinase isoform p110delta is required for glioma cell migration and invasion..Eur J Cancer2012;48:149-57

[83]

Guerreiro AS,Kulesza DW,Elsing AN,Jackson SP,Grotzer MA,Arcaro A.A sensitized RNA interference screen identifies a novel role for the PI3K p110gamma isoform in medulloblastoma cell proliferation and chemoresistance..Mol Cancer Res2011;9:925-35

[84]

Boller D,De Laurentiis A,Marinov M,Depledge P,Saghir N,Kaizawa H,Ohishi T,Delattre O,Höland K,Frei K,Waterfield MD.Targeting PI3KC2beta impairs proliferation and survival in acute leukemia, brain tumours and neuroendocrine tumours..Anticancer Res2012;32:3015-27

[85]

Ehrhardt M,Holst MI,Dilloo D.The PI3K inhibitor GDC-0941 displays promising in vitro and in vivo efficacy for targeted medulloblastoma therapy..Oncotarget2015;6:802-13 PMCID:PMC4359256

[86]

Hartmann W,Koch A,Endl E,Denkhaus D,Sörensen N,Pietsch T.Phosphatidylinositol 3'-kinase/AKT signaling is activated in medulloblastoma cell proliferation and is associated with reduced expression of PTEN..Clin Cancer Res2006;12:3019-27

[87]

Koul D,Bergh S,Shishodia S,Lu Y,Mills GB.Inhibition of Akt survival pathway by a small-molecule inhibitor in human glioblastoma..Mol Cancer Ther2006;5:637-44

[88]

Gallia GL,Hann CL,Giranda VL,Brem H.Inhibition of Akt inhibits growth of glioblastoma and glioblastoma stem-like cells..Mol Cancer Ther2009;8:386-93 PMCID:PMC4498795

[89]

Kumar A,Kadian R,Tye GW.The alkylphospholipid perifosine induces apoptosis and p21-mediated cell cycle arrest in medulloblastoma..Mol Cancer Res2009;7:1813-21

[90]

Becher OJ,Walker TR,Nazarian J,Hiner RL,Huse JT,MacDonald TJ.Preclinical evaluation of radiation and perifosine in a genetically and histologically accurate model of brainstem glioma..Cancer Res2010;70:2548-57 PMCID:PMC3831613

[91]

Knobbe CB.Genetic alterations and aberrant expression of genes related to the phosphatidyl-inositol-3'-kinase/protein kinase B (Akt) signal transduction pathway in glioblastomas..Brain Pathol2003;13:507-18

[92]

Vitucci M,Bash RE,Schmid RS,McNeill RS,Wang S,Miller CR.Cooperativity between MAPK and PI3K signaling activation is required for glioblastoma pathogenesis..Neuro Oncol2013;15:1317-29 PMCID:PMC3779038

[93]

Dey N,De P,Peng Q,Durden DL.The protein phosphatase activity of PTEN regulates SRC family kinases and controls glioma migration..Cancer Res2008;68:1862-71

[94]

Mayo LD,Durden DL,Donner DB.PTEN protects p53 from Mdm2 and sensitizes cancer cells to chemotherapy..J Biol Chem2002;277:5484-9

[95]

Merrill MJ.Insulin-like growth factor-I receptors in human glial tumors..J Clin Endocrinol Metab1990;71:199-209

[96]

Sinha S,Dixit D,Sen E.IGF-1 induced HIF-1alpha-TLR9 cross talk regulates inflammatory responses in glioma..Cell Signal2011;23:1869-75

[97]

Lin YC,Hung CM,Liu LC,Kao JY,Way TD.Osthole inhibits insulin-like growth factor-1-induced epithelial to mesenchymal transition via the inhibition of PI3K/Akt signaling pathway in human brain cancer cells..J Agric Food Chem2014;62:5061-71

[98]

Yin S,Stromberg T,Andersson S,Ericsson C,Nistér M,Ekström TJ.Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma..Neuro Oncol2010;12:19-27 PMCID:PMC2940558

[99]

Maris C,Trepant AL,Sauvage S,Rorive S,Decaestecker C.IGF-IR: a new prognostic biomarker for human glioblastoma..Br J Cancer2015;113:729-37

[100]

Kong DS,Kim DH,Yoo JS,Suh YL,Park K,Nam DH.Prognostic significance of c-Met expression in glioblastomas..Cancer2009;115:140-8

[101]

Fixman ED,Kamikura DM,Park M.Pathways downstream of Shc and Grb2 are required for cell transformation by the tpr-Met oncoprotein..J Biol Chem1996;271:13116-22

[102]

Graziani A,Cantley LC.1991. The tyrosine-phosphorylated hepatocyte growth factor/scatter factor receptor associates with phosphatidylinositol 3-kinase..J Biol Chem1991;266:22087-90

[103]

Li Y,Kwon S,Saldanha U,Kuchner EB,Laterra J.The scatter factor/hepatocyte growth factor: c-met pathway in human embryonal central nervous system tumor malignancy..Cancer Res2005;65:9355-62

[104]

Martens T,Eckerich C,Merchant M,Westphal M.A novel one-armed anti-c-Met antibody inhibits glioblastoma growth in vivo..Clin Cancer Res2006;12:6144-52

[105]

Lu KV,Parachoniak CA,Aghi MK,Isachenko N,Phillips JJ,Park M.VEGF inhibits tumor cell invasion and mesenchymal transition through a MET/VEGFR2 complex..Cancer cell2012;22:21-35 PMCID:PMC4068350

[106]

Kongkham PN,Smith CA.Inhibition of the MET Receptor Tyrosine Kinase as a Novel Therapeutic Strategy in Medulloblastoma..Transl Oncol2010;3:336-43 PMCID:PMC3000458

[107]

Faria CC,Dubuc AM,Diaz RJ,Luck A,Olsen S,Garzia L,Mack SC,Reynaud D,Post M,Pfister SM,Kool M,Smith CA,Rutka JT.Foretinib is effective therapy for metastatic sonic hedgehog medulloblastoma..Cancer Res2015;75:134-46

[108]

Lv B,Lv S,Fan K,Wang F,Ma X,Xu K,Wang G,Zhang L.CXCR4 Signaling Induced Epithelial-Mesenchymal Transition by PI3K/AKT and ERK Pathways in Glioblastoma..Mol Neurobiol2015;52:1263-8

[109]

Kil WJ,Camphausen K.Post-radiation increase in VEGF enhances glioma cell motility in vitro..Radiat Oncol2012;7:25 PMCID:PMC3307492

[110]

Westhoff MA,Bruhl O,La Ferla-Bruhl K,Nonnenmacher L.A critical evaluation of PI3K inhibition in Glioblastoma and Neuroblastoma therapy..Mol Cell Ther2014;2:32 PMCID:PMC4452069

[111]

Birks DK,Donson AM,Vibhakar R.Survey of MicroRNA expression in pediatric brain tumors..Pediatr Blood Cancer2011;56:211-6

[112]

Pang JC,Chen Z.Oncogenic role of microRNAs in brain tumors..Acta Neuropathol2009;117:599-611

[113]

Weeraratne SD,Teider N,Winter D,Sengupta S,Remke M,Warren P,Steen JA,Cho YJ.Pleiotropic effects of miR-183~96~182 converge to regulate cell survival, proliferation and migration in medulloblastoma..Acta Neuropathol2012;123:539-52

[114]

Stamenkovic I.Matrix metalloproteinases in tumor invasion and metastasis..Semin Cancer Biol2000;10:415-33

[115]

Vu TH.Matrix metalloproteinases: effectors of development and normal physiology..Genes Dev2000;14:2123-33

[116]

Chen JS,Fu XH,Chen XL,Chen LZ,Li W,Zhang LJ.Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: Association with MMP-9..Hepatol Res2009;39:177-86

[117]

Jiao Y,Liu Y,Xu X,Wang S,Li Y.Resveratrol Inhibits the Invasion of Glioblastoma-Initiating Cells via Down-Regulation of the PI3K/Akt/NF-kappaB Signaling Pathway..Nutrients2015;7:4383-402

[118]

Greenspoon JN,Hirte H,Devillers R,Whitton A.Fractionated stereotactic radiosurgery with concurrent temozolomide chemotherapy for locally recurrent glioblastoma multiforme: a prospective cohort study..Onco Targets Ther2014;7:485-90 PMCID:PMC3969344

[119]

Kim S,Lin WW,Grivennikov S,Luo JL.Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis..Nature2009;457:102-6 PMCID:PMC2746432

[120]

Du R,Petritsch C,Ganss R,Song H,Johnson RS,Bergers G.HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion..Cancer cell2008;13:206-20 PMCID:PMC2643426

[121]

Mantovani A,Sica A.Cancer-related inflammation..Nature2008;454:436-44

[122]

Coussens LM.Zitvogel L, Palucka AK. Neutralizing tumor-promoting chronic inflammation: A magic bullet? (vol 339, pg 286, 2013)..Science2013;339:286-91

[123]

Schmid MC,Kang SW,Quilliam LA.PI3-kinase gamma promotes Rap1a-mediated activation of myeloid cell integrin alpha4beta1, leading to tumor inflammation and growth..PloS one2013;8:e60226

[124]

Rommel C,Ji H.PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond? Nature reviews..Immunology2007;7:191-201

[125]

Kettenmann H,Noda M.Physiology of microglia..Physiol Rev2011;91:461-553

[126]

Wei J,Heimberger A.The controversial role of microglia in malignant gliomas..Clin Dev Immunol2013;2013:285246 PMCID:PMC3741958

[127]

Markovic DS,Chirasani S,Raguet H,Sliwa M,Kälin R,Holmbeck K,Kiwit J,Lehnardt S,Glass R.Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion..Proc Natl Acad Sci U S A2009;106:12530-5 PMCID:PMC2718387

[128]

Ellert-Miklaszewska A,Lipko M,Maleszewska M.Molecular definition of the pro-tumorigenic phenotype of glioma-activated microglia..Glia2013;61:1178-90

[129]

Lisi L,Navarra P.The mTOR kinase inhibitors polarize glioma-activated microglia to express a M1 phenotype..J Neuroinflammation2014;11:125 PMCID:PMC4128534

[130]

Margol AS,Gnanachandran J,Kennedy RJ,Dhall G,Erdreich-Epstein A,Drissi R,Gilles FH,Sposto R.Tumor-associated macrophages in SHH subgroup of medulloblastomas..Clin Cancer Res2015;21:1457-65

[131]

Sampaio NG,Cox D,Condeelis J,Pixley FJ.Phosphorylation of CSF-1R Y721 mediates its association with PI3K to regulate macrophage motility and enhancement of tumor cell invasion..J Cell Sci2011;124:2021-31 PMCID:PMC3104034

[132]

Mouchemore KA,Murrey MW,Lannutti BJ.Specific inhibition of PI3K p110delta inhibits CSF-1-induced macrophage spreading and invasive capacity..FEBS J2013;280:5228-36 PMCID:PMC3773002

[133]

Carrasco-Garcia E,Martinez-Lacaci I.Role of receptor tyrosine kinases and their ligands in glioblastoma..Cells2014;3:199-235 PMCID:PMC4092852

[134]

Chi AS.Inhibiting kinases in malignant gliomas..Expert Opin Ther Targets2007;11:473-96

[135]

De Witt Hamer PC.Small molecule kinase inhibitors in glioblastoma: a systematic review of clinical studies..Neuro Oncol2010;12:304-16 PMCID:PMC2940593

[136]

Arteaga CL.Tyrosine kinase inhibitors: why does the current process of clinical development not apply to them?.Cancer cell2004;5:525-31

[137]

Cloughesy TF,Nghiemphu P,Dang J,Hsueh T,Wang W,Liau L,Becker D,Lai A,Oglesby T,Trent J,Mischel PS,Sawyers CL.Antitumor activity of rapamycin in a Phase I trial for patients with recurrent PTEN-deficient glioblastoma..PLoS Med2008;5:e8

[138]

Trail data from ClinicalTrails.gov [Interent]. New York: U.S. National Institutes of Health. Available from: https://clinicaltrials.gov/

AI Summary AI Mindmap
PDF

31

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/