FGFR1 Induces Glioblastoma Radioresistance through the PLCγ/Hif1α Pathway.

Abstract:

:FGF2 signaling in glioblastoma induces resistance to radiotherapy, so targeting FGF2/FGFR pathways might offer a rational strategy for tumor radiosensitization. To investigate this possibility, we evaluated a specific role for FGFR1 in glioblastoma radioresistance as modeled by U87 and LN18 glioblastomas in mouse xenograft models. Silencing FGFR1 decreased radioresistance in a manner associated with radiation-induced centrosome overduplication and mitotic cell death. Inhibiting PLCγ (PLCG1), a downstream effector signaling molecule for FGFR1, was sufficient to produce similar effects, arguing that PLCγ is an essential mediator of FGFR1-induced radioresistance. FGFR1 silencing also reduced expression of HIF1α, which in addition to its roles in hypoxic responses exerts an independent effect on radioresistance. Finally, FGFR1 silencing delayed the growth of irradiated tumor xenografts, in a manner that was associated with reduced HIF1α levels but not blood vessel alterations. Taken together, our results offer a preclinical proof of concept that FGFR1 targeting can degrade radioresistance in glioblastoma, a widespread problem in this tumor, prompting clinical investigations of the use of FGFR1 inhibitors for radiosensitization. Cancer Res; 76(10); 3036-44. ©2016 AACR.

journal_name

Cancer Res

journal_title

Cancer research

authors

Gouazé-Andersson V,Delmas C,Taurand M,Martinez-Gala J,Evrard S,Mazoyer S,Toulas C,Cohen-Jonathan-Moyal E

doi

10.1158/0008-5472.CAN-15-2058

subject

Has Abstract

pub_date

2016-05-15 00:00:00

pages

3036-44

issue

10

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-15-2058

journal_volume

76

pub_type

杂志文章
  • Modulation by retinoic acid (RA) of squamous cell differentiation, cellular RA-binding proteins, and nuclear RA receptors in human head and neck squamous cell carcinoma cell lines.

    abstract::The ability of all-trans-retinoic acid (RA) to modulate the growth and squamous differentiation of four head and neck squamous cell carcinoma cell lines (183, 886, 1483, and SqCC/Y1) was examined, and the relationship of their state of squamous differentiation and RA responsiveness to the expression of cytosolic RA-bi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Zou CP,Clifford JL,Xu XC,Sacks PG,Chambon P,Hong WK,Lotan R

    更新日期:1994-10-15 00:00:00

  • Expression of N-myc and c-src during the development of fetal human brain.

    abstract::We studied N-myc RNA by in situ hybridization and S1 nuclease protection analysis in human fetal cerebrum, retina, lung, liver, and placenta during the second trimester. High levels of N-myc RNA were found in the early fetal cerebral germinal layer and the primordial cortex, with lower levels in the intermediate layer...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Grady EF,Schwab M,Rosenau W

    更新日期:1987-06-01 00:00:00

  • A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells.

    abstract::GW572016 (Lapatinib) is a tyrosine kinase inhibitor in clinical development for cancer that is a potent dual inhibitor of epidermal growth factor receptor (EGFR, ErbB-1) and ErbB-2. We determined the crystal structure of EGFR bound to GW572016. The compound is bound to an inactive-like conformation of EGFR that is ver...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-1168

    authors: Wood ER,Truesdale AT,McDonald OB,Yuan D,Hassell A,Dickerson SH,Ellis B,Pennisi C,Horne E,Lackey K,Alligood KJ,Rusnak DW,Gilmer TM,Shewchuk L

    更新日期:2004-09-15 00:00:00

  • SMYD3-Mediated H2A.Z.1 Methylation Promotes Cell Cycle and Cancer Proliferation.

    abstract::SMYD3 methyltransferase is nearly undetectable in normal human tissues but highly expressed in several cancers, including breast cancer, although its contributions to pathogenesis in this setting are unclear. Here we report that histone H2A.Z.1 is a substrate of SMYD3 that supports malignancy. SMYD3-mediated dimethyla...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-16-0500

    authors: Tsai CH,Chen YJ,Yu CJ,Tzeng SR,Wu IC,Kuo WH,Lin MC,Chan NL,Wu KJ,Teng SC

    更新日期:2016-10-15 00:00:00

  • Ras oncogene-induced sensitization to 1-beta-D-arabinofuranosylcytosine.

    abstract::Human tumor cells containing ras oncogenes display enhanced sensitivity to 1-beta-D-arabinofuranosylcytosine (Ara-C) and other deoxycytidine analogues (H-M. Koo, et al., Cancer Res., 56: 5211-5216, 1996). Human tumor cell lines with or without a ras oncogene as well as a pair of isogenic cell lines with one containing...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Koo HM,McWilliams MJ,Alvord WG,Vande Woude GF

    更新日期:1999-12-15 00:00:00

  • Batracylin (NSC 320846), a dual inhibitor of DNA topoisomerases I and II induces histone gamma-H2AX as a biomarker of DNA damage.

    abstract::Batracylin (8-aminoisoindolo [1,2-b]quinazolin-10(12H)-one; NSC320846) is an investigational clinical anticancer agent. Previous animal studies showed activity against solid tumors and Adriamycin-resistant leukemia. We initially sought to test the proposed Top2-mediated DNA cleavage activity of batracylin and identify...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-0804

    authors: Rao VA,Agama K,Holbeck S,Pommier Y

    更新日期:2007-10-15 00:00:00

  • Epidermal growth factor receptor-targeted immunophotodiagnosis and photoimmunotherapy of oral precancer in vivo.

    abstract::Immunophotodiagnosis uses a fluorescence-labeled monoclonal antibody (MAb) that recognizes a tumor-associated antigen to image the fluorescence emitted from the fluorophore-bound MAb that has localized in the tissue. It may be used to diagnose malignant or precancerous lesions, to delineate the margins for tumor resec...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Soukos NS,Hamblin MR,Keel S,Fabian RL,Deutsch TF,Hasan T

    更新日期:2001-06-01 00:00:00

  • Concomitant tumor and minor histocompatibility antigen-specific immunity initiate rejection and maintain remission from established spontaneous solid tumors.

    abstract::Nonmyeloablative hematopoietic cell transplantation can cure patients with hematologic malignancies but has reported limited success against solid tumors. This is possibly because of profound peripheral tolerance mechanisms and/or suboptimal tumor recognition by effector T lymphocytes. We report that in mice developin...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-4253

    authors: Hess Michelini R,Freschi M,Manzo T,Jachetti E,Degl'Innocenti E,Grioni M,Basso V,Bonini C,Simpson E,Mondino A,Bellone M

    更新日期:2010-05-01 00:00:00

  • Induction by some protein kinase inhibitors of differentiation of a mouse megakaryoblastic cell line established by coinfection with Abelson murine leukemia virus and recombinant SV40 retrovirus.

    abstract::Mouse C1 line cells are megakaryoblastic cells established by coinfection of Abelson murine leukemia virus and recombinant simian virus 40. We examined the effects of various compounds on growth and differentiation of these cells. Megakaryocytic differentiation of C1 cells was not induced by cytokines that stimulate m...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Honma Y,Okabe-Kado J,Kasukabe T,Hozumi M,Kajigaya S,Suda T,Miura Y

    更新日期:1991-09-01 00:00:00

  • Gefitinib reverses TRAIL resistance in human bladder cancer cell lines via inhibition of AKT-mediated X-linked inhibitor of apoptosis protein expression.

    abstract::In a previous study, we found that the small-molecule epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839, Iressa) blocked cell proliferation at biologically relevant concentrations in approximately one third (6 of 17) of human bladder cancer cell lines examined. Here, we studied the effects of gefitin...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-1224

    authors: Shrader M,Pino MS,Lashinger L,Bar-Eli M,Adam L,Dinney CP,McConkey DJ

    更新日期:2007-02-15 00:00:00

  • Carcinogen-induced lesions in the rat pancreas: effects of varying levels of essential fatty acid.

    abstract::The ingestion of high levels of fats, especially unsaturated fats, has been shown to enhance carcinogenesis in a variety of experimental model systems. Recently attention has focused upon the unsaturated linoleic fatty acid (18:2 omega 6) as a key component for this postinitiation enhancement. We have investigated the...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Roebuck BD,Longnecker DS,Baumgartner KJ,Thron CD

    更新日期:1985-11-01 00:00:00

  • Association of cyst type with risk factors for breast cancer and relapse rate in women with gross cystic disease of the breast.

    abstract::The concentration of potassium (K+) and sodium (Na+) was measured in breast cyst fluid (BCF) from 611 cysts greater than 3 ml aspirated in 520 women with gross cystic disease of the breast. These women were enrolled, from 1983 on, in a cohort study aimed at assessing the relationship between cyst type, as defined by t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Naldoni C,Costantini M,Dogliotti L,Bruzzi P,Bucchi L,Buzzi G,Torta M,Angeli A

    更新日期:1992-04-01 00:00:00

  • Covalent binding of benzidine and N-acetylbenzidine to DNA at the C-8 atom of deoxyguanosine in vivo and in vitro.

    abstract::Benzidine, a human urinary bladder carcinogen, induces hepatic tumors in mice and rats. In this study, [3H]benzidine was administered in drinking water to mice for 1 week, and the covalent binding of the carcinogen to hepatic DNA was then determined. A single carcinogen:DNA adduct was detected which decreased in conce...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Martin CN,Beland FA,Roth RW,Kadlubar FF

    更新日期:1982-07-01 00:00:00

  • Heterogeneous expression of melanoma-associated antigens and HLA antigens by primary and multiple metastatic lesions removed from patients with melanoma.

    abstract::Indirect immunofluorescence staining with a large battery of monoclonal antibodies of primary and autologous metastatic lesions removed from seven patients with melanoma has detected heterogeneity in the expression of various types of melanoma-associated antigens (MAAs), of distinct determinants of the high molecular ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Natali P,Bigotti A,Cavaliere R,Liao SK,Taniguchi M,Matsui M,Ferrone S

    更新日期:1985-06-01 00:00:00

  • Effect of type and amount of dietary fat on the enhancement of rat mammary tumorigenesis by exercise.

    abstract::The effect(s) of treadmill exercise and type and amount of dietary fat on the process of mammary tumorigenesis was investigated. Female Sprague-Dawley rats were fed a purified 5% fat diet (AIN-76A) from 21 to 64 days of age. At 50 days of age each rat was intubated p.o. with 5 mg 7,12-dimethylbenz(a)anthracene (DMBA)....

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Thompson HJ,Ronan AM,Ritacco KA,Tagliaferro AR

    更新日期:1989-04-15 00:00:00

  • Unilateral chromatid damage: a new basis for 6-thioguanine cytotoxicity.

    abstract::Using the technique of premature chromosome condensation, which permits the visual inspection of interphase chromatin, we have shown previously that 28 hr after exposure to 6-thioguanine (TG) specific and drastic morphological changes in the chromosomes of Chinese hamster ovary fibroblasts in the G2 phase of the cell ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Maybaum J,Mandel HG

    更新日期:1983-08-01 00:00:00

  • Maleic vinyl ether activation of murine macrophages against lung-metastasizing tumors.

    abstract::A 16,500 molecular weight fraction of maleic vinyl ether (MVE-2) induced tumoristatic and tumoricidal activity in peritoneal macrophages of BALB/c and C57BL/6 mice following i.p. administration. Growth of B16 melanoma cells in vitro was inhibited up to 85% by MVE-2-activated, but not resident, peritoneal macrophages. ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Loveless SE,Munson AE

    更新日期:1981-10-01 00:00:00

  • p38 Stabilizes Snail by Suppressing DYRK2-Mediated Phosphorylation That Is Required for GSK3β-βTrCP-Induced Snail Degradation.

    abstract::Snail is a key regulator of epithelial-mesenchymal transition (EMT), which is a major step in tumor metastasis. Although the induction of Snail transcription precedes EMT, posttranslational regulation, especially phosphorylation of Snail, is critical for determining Snail protein levels or stability, subcellular local...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-0049

    authors: Ryu KJ,Park SM,Park SH,Kim IK,Han H,Kim HJ,Kim SH,Hong KS,Kim H,Kim M,Yoon SJ,Asaithambi K,Lee KH,Park JY,Hah YS,Cho HJ,Yook JI,Yang JW,Ko GH,Lee G,Kang YJ,Hwangbo C,Kim KD,Park YJ,Yoo J

    更新日期:2019-08-15 00:00:00

  • Medullary thyroid carcinoma arises in the absence of prolactin signaling.

    abstract::Prolactin, a pituitary hormone, exerts pleiotropic effects in various cells. These effects are mediated by a membrane receptor highly expressed in many tissues. To analyze prolactin effects on the thyroid gland, we first identified prolactin receptor (PRLR) mRNAs by in situ hybridization. To further evaluate the physi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-3937

    authors: Kedzia C,Lacroix L,Ameur N,Ragot T,Kelly PA,Caillou B,Binart N

    更新日期:2005-09-15 00:00:00

  • CC-chemokine ligand 20/macrophage inflammatory protein-3α and CC-chemokine receptor 6 are overexpressed in myeloma microenvironment related to osteolytic bone lesions.

    abstract::The expression of the chemokine CC-chemokine ligand 20 (CCL20)/macrophage inflammatory protein (MIP)-3alpha and its receptor CC-chemokine receptor 6 (CCR6) by multiple myeloma (MM) and microenvironment cells and their potential relationship with osteoclast (OC) formation and osteolytic bone lesions in MM patients was ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-0402

    authors: Giuliani N,Lisignoli G,Colla S,Lazzaretti M,Storti P,Mancini C,Bonomini S,Manferdini C,Codeluppi K,Facchini A,Rizzoli V

    更新日期:2008-08-15 00:00:00

  • A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation.

    abstract::MicroRNAs (miRNAs) are small noncoding RNAs, thought to be involved in physiologic and developmental processes by negatively regulating expression of target genes. We have previously reported frequent down-regulation of the let-7 miRNA family in lung cancers and, in the present study, assessed alteration in a panel of...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-2352

    authors: Hayashita Y,Osada H,Tatematsu Y,Yamada H,Yanagisawa K,Tomida S,Yatabe Y,Kawahara K,Sekido Y,Takahashi T

    更新日期:2005-11-01 00:00:00

  • Combined immunostimulation and conditional cytotoxic gene therapy provide long-term survival in a large glioma model.

    abstract::In spite of preclinical efficacy and recent randomized, controlled studies with adenoviral vectors expressing herpes simplex virus-1 thymidine kinase (HSV1-TK) showing statistically significant increases in survival, most clinical trials using single therapies have failed to provide major therapeutic breakthroughs. Be...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-3434

    authors: Ali S,King GD,Curtin JF,Candolfi M,Xiong W,Liu C,Puntel M,Cheng Q,Prieto J,Ribas A,Kupiec-Weglinski J,van Rooijen N,Lassmann H,Lowenstein PR,Castro MG

    更新日期:2005-08-15 00:00:00

  • Human ovarian carcinoma cells maintained on extracellular matrix versus plastic.

    abstract::The ability of culture dishes coated with an extracellular matrix (ECM) to act as a suitable substrate for human ovarian carcinoma cells in vitro has been examined. The plating efficiency on ECM was 30 to 80% (dispersed tumor cells from solid tumor tissue and effusions) with active proliferation of tumor cells being o...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Crickard K,Crickard U,Yoonessi M

    更新日期:1983-06-01 00:00:00

  • Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion.

    abstract::Donor lymphocyte infusions (DLI) provide effective therapy for patients with multiple myeloma who have relapsed after allogeneic bone marrow transplantation. However, the immunological mechanisms of the graft-versus-myeloma (GVM) effect have not been defined, and the target antigens of this response have not been iden...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Orsini E,Bellucci R,Alyea EP,Schlossman R,Canning C,McLaughlin S,Ghia P,Anderson KC,Ritz J

    更新日期:2003-05-15 00:00:00

  • Comparative dual label study of first and second generation antitumor-associated glycoprotein-72 monoclonal antibodies in colorectal cancer patients.

    abstract::Radiolabeled first-generation anti-tumor-associated glycoprotein-72 (TAG-72) monoclonal antibody (MAb), B72.3, has proven useful in detecting primary and secondary colorectal carcinoma. It has been anticipated that the development of second-generation, higher affinity, anti-TAG-72 MAbs, CC49 and CC83, would be of grea...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gallinger S,Reilly RM,Kirsh JC,Odze RD,Schmocker BJ,Hay K,Polihronis J,Damani MT,Shpitz B,Stern HS

    更新日期:1993-01-15 00:00:00

  • Complement Activation via a C3a Receptor Pathway Alters CD4+ T Lymphocytes and Mediates Lung Cancer Progression.

    abstract::The complement cascade is a part of the innate immune system that acts primarily to remove pathogens and injured cells. However, complement activation is also peculiarly associated with tumor progression. Here we report mechanistic insights into this association in multiple immunocompetent orthotopic models of lung ca...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-17-0240

    authors: Kwak JW,Laskowski J,Li HY,McSharry MV,Sippel TR,Bullock BL,Johnson AM,Poczobutt JM,Neuwelt AJ,Malkoski SP,Weiser-Evans MC,Lambris JD,Clambey ET,Thurman JM,Nemenoff RA

    更新日期:2018-01-01 00:00:00

  • Transforming growth factor beta induces clustering of HER2 and integrins by activating Src-focal adhesion kinase and receptor association to the cytoskeleton.

    abstract::It has been proposed that cross talk between integrin and growth factor receptor signaling such as ErbB2 (HER2) is required for activation of downstream effectors and ErbB2-mediated mammary tumorigenesis. Here we show that transforming growth factor beta (TGF-beta) induced focal adhesion kinase (FAK)-dependent cluster...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-2649

    authors: Wang SE,Xiang B,Zent R,Quaranta V,Pozzi A,Arteaga CL

    更新日期:2009-01-15 00:00:00

  • Multiple roles of p53-related pathways in somatic cell reprogramming and stem cell differentiation.

    abstract::The inactivation of p53 functions enhances the efficiency and decreases the latency of producing induced pluripotent stem cells (iPSC) in culture. The formation of iPSCs in culture starts with a rapid set of cell divisions followed by an epigenetic reprogramming of the DNA and chromatin. The mechanisms by which the p5...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-1451

    authors: Yi L,Lu C,Hu W,Sun Y,Levine AJ

    更新日期:2012-11-01 00:00:00

  • Mapping extracellular pH in rat brain gliomas in vivo by 1H magnetic resonance spectroscopic imaging: comparison with maps of metabolites.

    abstract::The value of extracellular pH (pH(e)) in tumors is an important factor in prognosisand choice of therapy. We demonstrate here that pH(e) can be mappedin vivo in a rat brain glioma by (1)H magnetic resonance spectroscopic imaging (SI) of the pH buffer (+/-)2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA). (1)H SI...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: García-Martín ML,Hérigault G,Rémy C,Farion R,Ballesteros P,Coles JA,Cerdán S,Ziegler A

    更新日期:2001-09-01 00:00:00

  • Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers.

    abstract::We previously demonstrated that mutational inactivation of transforming growth factor beta type II receptors (RIIs) is very common among the 13% of human colon cancers with microsatellite instability. These mutations principally cluster in the BAT-RII polyadenine sequence repeat. Among microsatellite stable (MSS) colo...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Grady WM,Myeroff LL,Swinler SE,Rajput A,Thiagalingam S,Lutterbaugh JD,Neumann A,Brattain MG,Chang J,Kim SJ,Kinzler KW,Vogelstein B,Willson JK,Markowitz S

    更新日期:1999-01-15 00:00:00