Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth.

Abstract:

:Malignant mesotheliomas (MMs) are very aggressive tumors that respond poorly to standard chemotherapeutic approaches. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in tumor aggressiveness, in part by mediating cell survival and reducing sensitivity to chemotherapy. Using antibodies recognizing the phosphorylated/activated form of AKT kinases, we observed elevated phospho-AKT staining in 17 of 26 (65%) human MM specimens. In addition, AKT phosphorylation was consistently observed in MMs arising in asbestos-treated mice and in MM cell xenografts. Consistent with reports implicating hepatocyte growth factor (HGF)/Met receptor signaling in MM, all 14 human and murine MM cell lines had HGF-inducible AKT activity. One of nine human MM cell lines had elevated AKT activity under serum-starvation conditions, which was associated with a homozygous deletion of PTEN, the first reported in MM. Treatment of this cell line with the mTOR inhibitor rapamycin resulted in growth arrest in G1 phase. Treatment of MM cells with the PI3K inhibitor LY294002 in combination with cisplatin had greater efficacy in inhibiting cell proliferation and inducing apoptosis than either agent alone. Collectively, these data indicate that MMs frequently express elevated AKT activity, which may be targeted pharmacologically to enhance chemotherapeutic efficacy. These findings also suggest that mouse models of MM may be useful for future preclinical studies of pharmaceuticals targeting the PI3K/AKT pathway.

journal_name

Oncogene

journal_title

Oncogene

authors

Altomare DA,You H,Xiao GH,Ramos-Nino ME,Skele KL,De Rienzo A,Jhanwar SC,Mossman BT,Kane AB,Testa JR

doi

10.1038/sj.onc.1208744

subject

Has Abstract

pub_date

2005-09-08 00:00:00

pages

6080-9

issue

40

eissn

0950-9232

issn

1476-5594

pii

1208744

journal_volume

24

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Signaling by dual specificity kinases.

    abstract::Dual specificity kinases that phosphorylate the Thr- and Tyr-residues within the TXY motif of MAP-kinases of play a central role in the regulation of various processes of cell growth. These dual specificity kinases also known as MAP kinase kinases are constituents of the sequential kinase signaling modules. Seven dist...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1202251

    authors: Dhanasekaran N,Premkumar Reddy E

    更新日期:1998-09-17 00:00:00

  • Estrogen-dependent sushi domain containing 3 regulates cytoskeleton organization and migration in breast cancer cells.

    abstract::Aromatase inhibitors (AIs) are the standard endocrine therapy for postmenopausal breast cancer; however, currently used biomarkers, such as, estrogen receptor-alpha/progesterone receptor (ERα/PR), predict only slightly more than half of the potential responders to AI treatment. To identify novel markers of AI responsi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.553

    authors: Moy I,Todorović V,Dubash AD,Coon JS,Parker JB,Buranapramest M,Huang CC,Zhao H,Green KJ,Bulun SE

    更新日期:2015-01-15 00:00:00

  • MDM2 expression is repressed by the RNA-binding protein RNPC1 via mRNA stability.

    abstract::The RNA-binding protein (RBP) RNPC1 is a target of the p53 family and forms a feedback regulatory loop with the p53 family proteins. The murine double minute-2 (MDM2) oncogene, a key negative regulator of p53, has a critical role in a variety of fundamental cellular processes. MDM2 expression is found to be regulated ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.238

    authors: Xu E,Zhang J,Chen X

    更新日期:2013-04-25 00:00:00

  • HPV16 E6 and E7 upregulate the histone lysine demethylase KDM2B through the c-MYC/miR-146a-5p axys.

    abstract::Persistent infection by high-risk human papillomaviruses (HPVs) is associated with the development of cervical cancer and a subset of anogenital and head and neck squamous cell carcinomas. Abnormal expression of cellular microRNAs (miRNAs) plays an important role in the development of cancer, including HPV-related tum...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-017-0083-1

    authors: Peta E,Sinigaglia A,Masi G,Di Camillo B,Grassi A,Trevisan M,Messa L,Loregian A,Manfrin E,Brunelli M,Martignoni G,Palù G,Barzon L

    更新日期:2018-03-01 00:00:00

  • Identification of NF-kappa B-regulated genes induced by TNFalpha utilizing expression profiling and RNA interference.

    abstract::Tumor necrosis factor alpha (TNF alpha) is a proinflammatory cytokine with important roles in regulating inflammatory responses as well as cell cycle proliferation and apoptosis. Although TNFalpha stimulates apoptosis, it also activates the transcription factor NF-kappa B, and studies have shown that inhibition of NF-...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206262

    authors: Zhou A,Scoggin S,Gaynor RB,Williams NS

    更新日期:2003-04-03 00:00:00

  • Systems biology analysis of G protein and MAP kinase signaling in yeast.

    abstract::Approximately a third of all drugs act by binding directly to cell surface receptors coupled to G proteins. Other drugs act indirectly on these same pathways, for example, by inhibiting neurotransmitter reuptake or by blocking the inactivation of intracellular second messengers. These drugs have revolutionized the tre...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1210416

    authors: Hao N,Behar M,Elston TC,Dohlman HG

    更新日期:2007-05-14 00:00:00

  • Midkine (MDK) growth factor: a key player in cancer progression and a promising therapeutic target.

    abstract::Midkine is a heparin-binding growth factor, originally reported as the product of a retinoic acid-responsive gene during embryogenesis, but currently viewed as a multifaceted factor contributing to both normal tissue homeostasis and disease development. Midkine is abnormally expressed at high levels in various human m...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/s41388-019-1124-8

    authors: Filippou PS,Karagiannis GS,Constantinidou A

    更新日期:2020-03-01 00:00:00

  • Activation of PDK-1 maintains mouse embryonic stem cell self-renewal in a PKB-dependent manner.

    abstract::The phosphatidylinositol 3' kinase (PI3K) pathway is involved in many cellular processes including cell proliferation, survival and glucose transport, and is implicated in various disease states, such as cancer and diabetes. Although there have been numerous studies dissecting the role of PI3K signaling in different c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.44

    authors: Ling LS,Voskas D,Woodgett JR

    更新日期:2013-11-21 00:00:00

  • Roles of heat shock factor 1 and 2 in response to proteasome inhibition: consequence on p53 stability.

    abstract::A single heat shock factor (HSF), mediating the heat shock response, exists from yeast to Drosophila, whereas several related HSFs have been found in mammals. This raises the question of the specific or redundant functions of the different members of the HSF family and in particular of HSF1 and HSF2, which are both ub...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.171

    authors: Lecomte S,Desmots F,Le Masson F,Le Goff P,Michel D,Christians ES,Le Dréan Y

    更新日期:2010-07-22 00:00:00

  • Mode of action of trabectedin in myxoid liposarcomas.

    abstract::To elucidate the mechanisms behind the high sensitivity of myxoid/round cell liposarcoma (MRCL) to trabectedin and the suggested selectivity for specific subtypes, we have developed and characterized three MRCL xenografts, namely ML017, ML015 and ML004 differing for the break point of the fusion gene FUS-CHOP, respect...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.462

    authors: Di Giandomenico S,Frapolli R,Bello E,Uboldi S,Licandro SA,Marchini S,Beltrame L,Brich S,Mauro V,Tamborini E,Pilotti S,Casali PG,Grosso F,Sanfilippo R,Gronchi A,Mantovani R,Gatta R,Galmarini CM,Sousa-Faro JM,D'Incalc

    更新日期:2014-10-30 00:00:00

  • Multimerin-2 is a ligand for group 14 family C-type lectins CLEC14A, CD93 and CD248 spanning the endothelial pericyte interface.

    abstract::The C-type lectin domain containing group 14 family members CLEC14A and CD93 are proteins expressed by endothelium and are implicated in tumour angiogenesis. CD248 (alternatively known as endosialin or tumour endothelial marker-1) is also a member of this family and is expressed by tumour-associated fibroblasts and pe...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.214

    authors: Khan KA,Naylor AJ,Khan A,Noy PJ,Mambretti M,Lodhia P,Athwal J,Korzystka A,Buckley CD,Willcox BE,Mohammed F,Bicknell R

    更新日期:2017-11-02 00:00:00

  • Tumorigenic activity of rho genes from Aplysia californica.

    abstract::rho genes have been found in both lower and higher eucaryotes. They code for proteins of 21 kDa, highly conserved in evolution, which belong to the superfamily of ras GTPases. Among the members of this superfamily there are proteins with a regulatory function, such as ras, and proteins involved in vesicular traffickin...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Perona R,Esteve P,Jiménez B,Ballestero RP,Ramón y Cajal S,Lacal JC

    更新日期:1993-05-01 00:00:00

  • How tumours escape mass destruction.

    abstract::It is now well established that the immune system can control neoplastic development and growth in a process termed immunosurveillance. A link between host immunosurveillance and neoplastic progression is revealed in cases where the immune response becomes compromised due to genetic or other pathological conditions, r...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2008.268

    authors: Stewart TJ,Abrams SI

    更新日期:2008-10-06 00:00:00

  • Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates.

    abstract::The motility of cancer cells in 3D matrices is of two types: mesenchymal motility, in which the cells are elongated and amoeboid motility, in which the cells are round. Amoeboid motility is driven by an actomyosin-based contractile force, which is regulated by the Rho/ROCK pathway. However, the molecular mechanisms un...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.2

    authors: Yamazaki D,Kurisu S,Takenawa T

    更新日期:2009-04-02 00:00:00

  • Novel synthetic bisindolylmaleimide alkaloids inhibit STAT3 activation by binding to the SH2 domain and suppress breast xenograft tumor growth.

    abstract::Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in malignant tumors and plays important roles in multiple aspects of cancer aggressiveness. Thus, targeting STAT3 promises to be an attractive strategy for the treatment of advanced metastatic tumors. Bisindolylmaleimide alkaloid (B...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-017-0076-0

    authors: Li X,Ma H,Li L,Chen Y,Sun X,Dong Z,Liu JY,Zhu W,Zhang JT

    更新日期:2018-05-01 00:00:00

  • Oncology studies using siRNA libraries: the dawn of RNAi-based genomics.

    abstract::High-throughput, human cell-based applications of RNA-mediated interference (RNAi) have emerged in recent years as perhaps the most powerful of a 'second wave' of functional genomics technologies. The available reagents and methodologies for RNAi screening studies now enable a wide range of different scopes and scales...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1208072

    authors: Sachse C,Echeverri CJ

    更新日期:2004-11-01 00:00:00

  • Wild-type p53 gene transfer is not detrimental to normal cells in vivo: implications for tumor gene therapy.

    abstract::The p53 oncosuppressor is strictly maintained in an inactive form under normal conditions, while it is post-translationally activated by a variety of stresses, enacting different protective biological functions. Since one critical issue in cancer gene therapy is tumor specificity, we asked whether the tight p53 regula...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207042

    authors: Bossi G,Mazzaro G,Porrello A,Crescenzi M,Soddu S,Sacchi A

    更新日期:2004-01-15 00:00:00

  • Merlin regulates transmembrane receptor accumulation and signaling at the plasma membrane in primary mouse Schwann cells and in human schwannomas.

    abstract::The NF2 gene product, merlin/schwannomin, is a cytoskeleton organizer with unique growth-inhibiting activity in specific cell types. A narrow spectrum of tumors is associated with NF2 deficiency, mainly schwannomas and meningiomas, suggesting cell-specific mechanisms of growth control. We have investigated merlin func...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.427

    authors: Lallemand D,Manent J,Couvelard A,Watilliaux A,Siena M,Chareyre F,Lampin A,Niwa-Kawakita M,Kalamarides M,Giovannini M

    更新日期:2009-02-12 00:00:00

  • The HMG-box transcription factor HBP1 is targeted by the pocket proteins and E1A.

    abstract::A yeast two-hybrid screen has identified HBP1 as a transcription factor capable of interacting with the pocket protein family. We show that HBP1 can interact with one of these, RB, both in vitro and in mammalian cells. Two distinct RB binding sites are present within HBP1--a high affinity binding site, mediated by an ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201243

    authors: Lavender P,Vandel L,Bannister AJ,Kouzarides T

    更新日期:1997-06-05 00:00:00

  • ARHI is a Ras-related small G-protein with a novel N-terminal extension that inhibits growth of ovarian and breast cancers.

    abstract::Our group recently identified Ras homolog member I (ARHI), a novel maternally imprinted tumor suppressor gene that encodes a 26 kDa GTP-binding protein with high homology to Ras and Rap. Unlike other Ras family members, ARHI exhibits several unusual structural and functional properties. ARHI contains a unique 34 amino...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206380

    authors: Luo RZ,Fang X,Marquez R,Liu SY,Mills GB,Liao WS,Yu Y,Bast RC

    更新日期:2003-05-15 00:00:00

  • The proximal signaling network of the BCR-ABL1 oncogene shows a modular organization.

    abstract::BCR-ABL1 is a fusion tyrosine kinase, which causes multiple types of leukemia. We used an integrated proteomic approach that includes label-free quantitative protein complex and phosphorylation profiling by mass spectrometry to systematically characterize the proximal signaling network of this oncogenic kinase. The pr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.331

    authors: Titz B,Low T,Komisopoulou E,Chen SS,Rubbi L,Graeber TG

    更新日期:2010-11-04 00:00:00

  • An integrative analysis reveals functional targets of GATA6 transcriptional regulation in gastric cancer.

    abstract::Lineage-restricted transcription factors (TFs) are frequently mutated or overexpressed in cancer and contribute toward malignant behaviors; however, the molecular bases of their oncogenic properties are largely unknown. As TF activities are difficult to inhibit directly with small molecules, the genes and pathways the...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.517

    authors: Sulahian R,Casey F,Shen J,Qian ZR,Shin H,Ogino S,Weir BA,Vazquez F,Liu XS,Hahn WC,Bass AJ,Chan V,Shivdasani RA

    更新日期:2014-12-04 00:00:00

  • Disabling the mitotic spindle and tumor growth by targeting a cavity-induced allosteric site of survivin.

    abstract::Survivin is a member of the inhibitor of apoptosis protein family and has an essential role in mitosis. Survivin is overexpressed in a large variety of human cancers and represents an attractive target for cancer therapy. Epidermal growth factor receptor and Her/neu-transformed human tumors in particular exhibit high ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.377

    authors: Berezov A,Cai Z,Freudenberg JA,Zhang H,Cheng X,Thompson T,Murali R,Greene MI,Wang Q

    更新日期:2012-04-12 00:00:00

  • Nrf2 and Nrf1 in association with Jun proteins regulate antioxidant response element-mediated expression and coordinated induction of genes encoding detoxifying enzymes.

    abstract::Antioxidant response element (ARE)-mediated expression and coordinated induction of genes encoding detoxifying enzymes is one mechanism of critical importance to cellular protection against oxidative stress. In the present report, we demonstrate that nuclear transcription factors Nrf2 and Nrf1 associate with Jun (c-Ju...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202237

    authors: Venugopal R,Jaiswal AK

    更新日期:1998-12-17 00:00:00

  • Characterization of p53 oligomerization domain mutations isolated from Li-Fraumeni and Li-Fraumeni like family members.

    abstract::p53 is a tumour suppressor gene which functions as a transcription factor to upregulate genes for growth arrest and apoptosis following DNA damage. p53 mutations are associated with Li-Fraumeni and Li-Fraumeni like syndromes. Recently mutations of the oligomerization domain have been isolated from an LFS and an LFL fa...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201974

    authors: Lomax ME,Barnes DM,Hupp TR,Picksley SM,Camplejohn RS

    更新日期:1998-08-06 00:00:00

  • The induction of uterine leiomyomas and mammary tumors in transgenic mice expressing polyomavirus (PyV) large T (LT) antigen is associated with the ability of PyV LT antigen to form specific complexes with retinoblastoma and CUTL1 family members.

    abstract::The inactivation of certain tumor suppressor genes is thought to play an important role in the genesis of a number of tumor types. For example, inactivation of the Retinoblastoma (Rb) tumor suppressor is frequently observed in a proportion of sporadic human breast cancers. While these studies suggest that inactivation...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1201707

    authors: Webster MA,Martin-Soudant N,Nepveu A,Cardiff RD,Muller WJ

    更新日期:1998-04-16 00:00:00

  • An activating mutation in the transmembrane domain of the granulocyte colony-stimulating factor receptor in patients with acute myeloid leukemia.

    abstract::To date, constitutively activating point mutations reported in hematopoietic growth factor receptors in patients with acute myeloid leukemia (AML) have been restricted to receptors with intrinsic tyrosine kinase activity such as c-kit and FLT3. We describe here a Thr617Asn mutation in the transmembrane domain of the n...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205767

    authors: Forbes LV,Gale RE,Pizzey A,Pouwels K,Nathwani A,Linch DC

    更新日期:2002-09-05 00:00:00

  • N-myc gene amplification in neuroblastoma is associated with altered phosphorylation of a proliferation related polypeptide (Op18).

    abstract::We have recently identified and cloned the gene for a cytosolic polypeptide, designated oncoprotein 18 (Op18), which is expressed in acute lymphocytic leukemia and some solid tumors including neuroblastoma. Op18 is phosphorylated upon treatment of lymphoid cells with phorbol myristate acetate. We have proposed that un...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Hailat N,Strahler J,Melhem R,Zhu XX,Brodeur G,Seeger RC,Reynolds CP,Hanash S

    更新日期:1990-11-01 00:00:00

  • Therapeutic approaches to AIDS-related malignancies.

    abstract::The introduction of highly active antiretroviral therapy (HAART) has changed dramatically the landscape of HIV disease. Deaths from AIDS-related diseases have been reduced by 75% since protease inhibitor therapy and combination antiretroviral therapy came into use in late 1995. While KS is declining, the situation for...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1206771

    authors: Berretta M,Cinelli R,Martellotta F,Spina M,Vaccher E,Tirelli U

    更新日期:2003-09-29 00:00:00

  • MHC class I dysfunction of glioma stem cells escapes from CTL-mediated immune response via activation of Wnt/β-catenin signaling pathway.

    abstract::Glioma stem cells (GSCs) decrease T cells cognition and evade systemic immunosurveillance via downregulations or defects of major histocompatibility complex class I (MHC-I) molecule and antigen-processing machinery (APM) components. Improvement of tumor surface antigens of GSCs may be effective strategy to trigger an ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-1045-6

    authors: Yang W,Li Y,Gao R,Xiu Z,Sun T

    更新日期:2020-01-01 00:00:00