Significance of FGF9 gene in resistance to anti-EGFR therapies targeting colorectal cancer: A subset of colorectal cancer patients with FGF9 upregulation may be resistant to anti-EGFR therapies.

Abstract:

:Although fibroblast growth factor (FGF) signals are strongly associated with malignancy, limited information is available regarding the role of the FGF9 signal in colorectal cancer (CRC). In this study, we investigated the frequency of FGF9 amplification in CRC clinical specimens and the association between the FGF9 gene and resistance to anti-EGFR therapies. In clinical samples, an FGF9 copy number gain of >5 copies was observed at a frequency of 8/145 (5.5%) and tended to be related to wild-type KRAS (7/96, 7.3%). Furthermore, FGF9 amplification was not observed in any of the samples from the 15 responders to anti-EGFR therapies but was observed in one sample from the seven non-responders with wild-type KRAS, and two samples from non-responders also had high FGF9 mRNA expression levels. FGF9 amplification was validated using a fluorescence in situ hybridization (FISH) analysis, and FGF9-amplified sections showed readily detectable signals originating from FGF9 protein when examined using immunohistochemistry. In both the in vitro and in vivo experiments using FGF9-overexpressing CRC cell lines, FGF9 overexpression induced strong resistance to anti-EGFR therapies via the enforced FGFR signal, and this resistance was cancelled by the application of an FGFR inhibitor. Considering these results, the FGF9 gene may play an important role in resistance to anti-EGFR therapies in patients with CRC, and such resistance might be overcome by combined treatment with an anti-FGFR inhibitor. These findings strongly encourage the development of FGFR-targeted therapy for CRC patients with FGF9 gene upregulation. © 2016 Wiley Periodicals, Inc.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Mizukami T,Togashi Y,Naruki S,Banno E,Terashima M,de Velasco MA,Sakai K,Yoneshige A,Hayashi H,Fujita Y,Tomida S,Nakajima TE,Fujino T,Boku N,Ito A,Nakagawa K,Nishio K

doi

10.1002/mc.22476

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

106-117

issue

1

eissn

0899-1987

issn

1098-2744

journal_volume

56

pub_type

杂志文章
  • Inhibition of proliferation and expression of T1 and cyclin D1 genes by thyroid hormone in mammary epithelial cells.

    abstract::The relationship between thyroid hormone (triiodothyronine, T(3)) and breast cancer is unclear. We studied the effect of the c-erbA/TR alpha proto-oncogene encoding a functional T(3) receptor (TR alpha 1), of its ligand T(3), and of its retroviral, mutated counterpart, the v-erbA oncogene, on the proliferation capacit...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.10046

    authors: González-Sancho JM,Figueroa A,López-Barahona M,López E,Beug H,Muñoz A

    更新日期:2002-05-01 00:00:00

  • Association of the EGFR intron 1 CA repeat length with lung cancer risk.

    abstract::Epidermal growth factor receptor (EGFR) plays an important role in the development and progression of lung cancer. A previous report noted that an increased number of polymorphic CA repeats in the first intron of the EGFR gene results in decreased transcriptional activity. To estimate the association of the length of ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20285

    authors: Zhang W,Weissfeld JL,Romkes M,Land SR,Grandis JR,Siegfried JM

    更新日期:2007-05-01 00:00:00

  • Common and distinct mechanisms of different redox-active carcinogens involved in the transformation of mouse JB6P+ cells.

    abstract::We transformed JB6P+ cells with prolonged intermittent low-dose UVB radiation or prolonged exposure to low-dose H(2)O(2) or CdCl(2). Stable transformation was confirmed by an anchorage-independence assay. The JB6P+ transformants formed more colonies (approximately six folds) in soft agar as compared to their JB6P+ par...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20410

    authors: Yang S,Misner B,Chiu R,Meyskens FL Jr

    更新日期:2008-07-01 00:00:00

  • Dishevelled-3 activates p65 to upregulate p120-catenin transcription via a p38-dependent pathway in non-small cell lung cancer.

    abstract::Dishevelled-3 (Dvl-3) and p120-catenin (p120ctn) have abnormal expression in non-small cell lung cancer (NSCLC), which is associated with poor prognosis. Dvl-3 upregulates p120ctn transcription in NSCLC cells, but the mechanism is unknown. Here we transiently transfected Dvl-3 cDNA to NSCLC cells. Dvl-3 transfection i...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22196

    authors: Zhao H,Zhao Y,Jiang G,Zhang X,Zhang Y,Dong Q,Luan L,Papavassiliou P,Wang E,Wang E

    更新日期:2015-06-01 00:00:00

  • Loss of heterozygosity on chromosomes 1, 11, 12, and 14 in hybrid mouse lung adenocarcinomas.

    abstract::An allelotype analysis of lung tumors in mouse hybrids was conducted to identify common regions of allelic loss. By using 50 informative genetic markers, the autosomes of 36 (A/J x C3H/HeJ) F1 adenocarcinomas were examined. Additional adenocarcinomas from as many as 72 (C3H/HeJ x A/J) F1 and 15 (BALB/cJ x DBA/2J) F1 h...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2744(199606)16:2<83::AID-MC4>3.

    authors: Herzog CR,Chen B,Wang Y,Schut HA,You M

    更新日期:1996-06-01 00:00:00

  • Involvement of protein kinase C α and δ activities on the induction of the retinoic acid system in mammary cancer cells.

    abstract::It has been established that retinoids exert some of their effects on cell differentiation and malignant phenotype reversion through the interaction with different members of the protein kinase C (PKC) family. Till nowadays the nature and extension of this interaction is not well understood. Due to the cytostatic and ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22181

    authors: Berardi DE,Bessone MI,Motter A,Bal de Kier Joffé ED,Urtreger AJ,Todaro LB

    更新日期:2015-10-01 00:00:00

  • Cisplatin resistance conferred by the RAD51D (E233G) genetic variant is dependent upon p53 status in human breast carcinoma cell lines.

    abstract::RAD51D, a paralog of the mammalian RAD51 gene, contributes towards maintaining genomic integrity by homologous recombination DNA repair and telomere maintenance. A RAD51D variant, E233G, was initially identified as a potential susceptibility allele in high-risk, site-specific, familial breast cancer. We describe in th...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20545

    authors: Nadkarni A,Rajesh P,Ruch RJ,Pittman DL

    更新日期:2009-07-01 00:00:00

  • Transforming activity of DNA from rat liver tumors induced by the carcinogen methyl(acetoxymethyl)nitrosamine.

    abstract::Altered c-Ha-ras genes have been frequently detected in the DNA of spontaneous or chemically induced mouse liver tumors. To determine if ras gene mutation is a frequent event during liver carcinogenesis in rats, we examined the transforming activity of DNA from liver tumors that developed in rats injected with methyl(...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940010108

    authors: Goyette M,Dolan M,Kaufmann W,Kaufman D,Shank PR,Fausto N

    更新日期:1988-01-01 00:00:00

  • Characterization of DNA-protein complexes induced in intact cells by the carcinogen chromate.

    abstract::Potassium chromate induced the formation of DNA-protein complexes in cultured Chinese hamster ovary cells. The DNA-protein complexes were isolated by ultracentrifugal sedimentation in the presence of 2% sodium dodecyl sulfate (SDS) and 5 M urea. Two-dimensional SDS-polyacrylamide gel electrophoresis analysis of the ch...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940010208

    authors: Miller CA 3rd,Costa M

    更新日期:1988-01-01 00:00:00

  • Putative tumor suppressor gene SEL1L was downregulated by aberrantly upregulated hsa-mir-155 in human pancreatic ductal adenocarcinoma.

    abstract::Sel-1-like (SEL1L) is a putative tumor suppressor gene that is significantly downregulated in human pancreatic ductal adenocarcinoma (PDA). The mechanism of the downregulation is unclear. Here, we investigated whether aberrantly upregulated microRNAs (miRNAs) repressed the expression of SEL1L. From reported miRNA micr...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22023

    authors: Liu Q,Chen J,Wang J,Amos C,Killary AM,Sen S,Wei C,Frazier ML

    更新日期:2014-09-01 00:00:00

  • Expression and localization of matrix-degrading metalloproteinases during colorectal tumorigenesis.

    abstract::The metalloproteinase matrilysin is widely expressed in the epithelial tumor cells of malignant colorectal adenocarcinomas. Approximately 50% of benign adenomas also express low levels of matrilysin that is focally localized. The expression of stromelysin-1, stromelysin-3, and gelatinase A was observed in the stromal ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940100404

    authors: Newell KJ,Witty JP,Rodgers WH,Matrisian LM

    更新日期:1994-08-01 00:00:00

  • Association between TP53 gene ARG72PRO polymorphism and chromosome aberrations in human cancers.

    abstract::It is well known that the TP53 gene considerably influences on DNA repair processes. Polymorphisms in the TP53 gene, particularly the well-known Arg72Pro in codon 72 of exon 4 (Ex4+119 G>C; rs1042522), can modify the functionality of the p53 protein and activation of DNA repair. Actually, polymorphic variants Arg and ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20633

    authors: Litviakov NV,Denisov EV,Takhauov RM,Karpov AB,Skobel'skaja EV,Vasil'eva EO,Goncharik OO,Ageeva AM,Mamonova NV,Mezheritskiy SA,Sevost'janova NV,Koshel AP

    更新日期:2010-06-01 00:00:00

  • Osteopontin induces multiple changes in gene expression that reflect the six "hallmarks of cancer" in a model of breast cancer progression.

    abstract::Tumor progression is a multistep process, which enables cells to evolve from benign to malignant tumors. This progression has been suggested to depend on six essential characteristics identified as the "hallmarks of cancer," which include: self-sufficiency in growth signals, insensitivity to growth-inhibitory signals,...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20105

    authors: Cook AC,Tuck AB,McCarthy S,Turner JG,Irby RB,Bloom GC,Yeatman TJ,Chambers AF

    更新日期:2005-08-01 00:00:00

  • Reduction in tamoxifen-induced CYP3A2 expression and DNA adducts using antisense technology.

    abstract::Tamoxifen (TAM) is widely used in the treatment and prevention of breast cancer. There is clear evidence that cytochrome P450 (CYP) 3A enzymes play an important role in TAM metabolism, resulting in metabolites that lead to formation of TAM-DNA adducts. We have investigated the effect of CYP3A2 antisense (AVI-4472) exp...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20143

    authors: Mahadevan B,Arora V,Schild LJ,Keshava C,Cate ML,Iversen PL,Poirier MC,Weston A,Pereira C,Baird WM

    更新日期:2006-02-01 00:00:00

  • Differential expression of Axl in hepatocellular carcinoma and correlation with tumor lymphatic metastasis.

    abstract::Protein kinases play important roles in tumor development and progression. A variety of members of the signal transduction enzymes serve as targets for therapeutic intervention in cancer. The dysregulation of Axl receptor and its ligand growth arrest-specific 6 (Gas6) is implicated in the pathogenesis of several cance...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20664

    authors: He L,Zhang J,Jiang L,Jin C,Zhao Y,Yang G,Jia L

    更新日期:2010-10-01 00:00:00

  • Transcriptional upregulation of MT2-MMP in response to hypoxia is promoted by HIF-1α in cancer cells.

    abstract::Hypoxia is a critical event in solid tumor development, invasion, and metastasis. Cellular adaptation to hypoxic microenvironment is essential for tumor progression and is largely mediated by hypoxia-inducible factor-1α (HIF-1α) through coordinated regulation of hypoxia-responsive genes. In this study, we found that m...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20678

    authors: Zhu S,Zhou Y,Wang L,Zhang J,Wu H,Xiong J,Zhang J,Tian Y,Wang C,Wu H

    更新日期:2011-10-01 00:00:00

  • Correlation of p53 immunoreactivity and sequencing in patients with glioma.

    abstract::This study examines the relationship between p53 immunostaining and direct sequencing of polymerase chain reaction (PCR) products in 61 gliomas. Glioma tissues obtained from patients at surgery were analyzed immunohistochemically with the monoclonal antibody PAb1801 to detect p53 protein abnormalities. Amplified p53 c...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2744(199601)15:1<1::AID-MC1>3.0

    authors: Kyritsis AP,Xu R,Bondy ML,Levin VA,Bruner JM

    更新日期:1996-01-01 00:00:00

  • Autophagy defects suggested by low levels of autophagy activator MAP1S and high levels of autophagy inhibitor LRPPRC predict poor prognosis of prostate cancer patients.

    abstract::MAP1S (originally named C19ORF5) is a widely distributed homolog of neuronal-specific MAP1A and MAP1B, and bridges autophagic components with microtubules and mitochondria to affect autophagosomal biogenesis and degradation. Mitochondrion-associated protein LRPPRC functions as an inhibitor for autophagy initiation to ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22193

    authors: Jiang X,Zhong W,Huang H,He H,Jiang F,Chen Y,Yue F,Zou J,Li X,He Y,You P,Yang W,Lai Y,Wang F,Liu L

    更新日期:2015-10-01 00:00:00

  • Cellular ubiquitination and proteasomal functions positively modulate mammalian nucleotide excision repair.

    abstract::The ubiquitin-proteasome pathway is fundamental to synchronized continuation of many cellular processes, for example, cell-cycle progression, stress response, and cell differentiation. Recent studies have shown that the ubiquitin-proteasome pathway functions in the regulation of nucleotide excision repair (NER) in yea...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20065

    authors: Wang QE,Wani MA,Chen J,Zhu Q,Wani G,El-Mahdy MA,Wani AA

    更新日期:2005-01-01 00:00:00

  • A superoxide anion generator, pyrogallol, inhibits the growth of HeLa cells via cell cycle arrest and apoptosis.

    abstract::We investigated the in vitro effects of pyrogallol on cell growth, cell cycle regulation, and apoptosis in HeLa cells. Pyrogallol inhibited the growth of HeLa cells with an IC(50) of approximately 45 microM. Pyrogallol induced arrest during all phases of the cell cycle and also very efficiently resulted in apoptosis i...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20369

    authors: Kim SW,Han YW,Lee ST,Jeong HJ,Kim SH,Kim IH,Lee SO,Kim DG,Kim SH,Kim SZ,Park WH

    更新日期:2008-02-01 00:00:00

  • Alterations in the expression of alpha6beta4 integrin and p21/WAF1/Cip1 in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis.

    abstract::Integrin alpha6beta4 is altered in many neoplastic cells, but no data exist to show this happens in esophageal neoplasms. To examine the expression of this integrin in rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine (NMBA), (alpha6 and beta4 expression was evaluated in normal esophageal epithelium, ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:

    authors: Khare L,Sabourin CL,DeYoung BR,Wagner BA,Stoner GD

    更新日期:1998-03-01 00:00:00

  • Aberrant expression and localization of connexin43 and connexin30 in a rat glioma cell line.

    abstract::Gap junctions are cellular structures which permit direct exchanges of small molecules from cytoplasm to cytoplasm in most of the cells of metazoan organisms. For four decades, it has been observed that the inhibition of this type of intercellular communication is often associated with tumorigenesis. The assumption th...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20393

    authors: Mennecier G,Derangeon M,Coronas V,Hervé JC,Mesnil M

    更新日期:2008-05-01 00:00:00

  • Targeting HSP60 by subcutaneous injections of jetPEI/HSP60-shRNA destabilizes cytoplasmic survivin and inhibits hepatocellular carcinoma growth.

    abstract::Heat shock protein 60 (HSP60) overexpresses in various types of cancer, but its expression levels and functions in hepatocellular carcinoma (HCC) are still in dispute. We aim to clarify this issue and examine whether HSP60 could be a therapeutic target for HCC. We found drastically enhanced cell apoptosis and suppress...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22827

    authors: Huang YH,Lin KH,Yu JS,Wu TJ,Lee WC,Chao CC,Pan TL,Yeh CT

    更新日期:2018-09-01 00:00:00

  • Energy balance modulates colon tumor growth: Interactive roles of insulin and estrogen.

    abstract::Obesity increases colorectal cancer (CRC) risk and progression. However, the impact of obesity on CRC in women is dependent on ovarian hormone status. The purpose of this study was to determine the interactive roles of obesity and ovarian hormones on serum markers of inflammation, cell signaling, and transplanted colo...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20720

    authors: Rondini EA,Harvey AE,Steibel JP,Hursting SD,Fenton JI

    更新日期:2011-05-01 00:00:00

  • Immunogenic cell death in colon cancer prevention and therapy.

    abstract::Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. The colonic mucosa constitutes a critical barrier and a major site of immune regulation. The immune system plays important roles in cancer development and treatment, and immune activation caused by chronic infection or inflammation is well-k...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1002/mc.23183

    authors: Ruan H,Leibowitz BJ,Zhang L,Yu J

    更新日期:2020-07-01 00:00:00

  • Targeting ERK beyond the boundaries of the kinase active site in melanoma.

    abstract::Extracellular signal-regulated kinase 1/2 (ERK1/2) constitute a point of convergence for complex signaling events that regulate essential cellular processes, including proliferation and survival. As such, dysregulation of the ERK signaling pathway is prevalent in many cancers. In the case of BRAF-V600E mutant melanoma...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1002/mc.23047

    authors: Sammons RM,Ghose R,Tsai KY,Dalby KN

    更新日期:2019-09-01 00:00:00

  • Correlation of increased levels of Ha-ras T24 protein with extent of loss of gap junction function in rat liver epithelial cells.

    abstract::Although it is known that cells transformed by ras and other oncogenes show reduced gap junction function, to date there has been no investigation of the quantitative relationship between intracellular levels of ras oncoprotein and loss of cell-cell communication. Using the rat liver epithelial cell line MTR6, which c...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940050307

    authors: de Feijter AW,Trosko JE,Krizman DB,Lebovitz RM,Lieberman MW

    更新日期:1992-01-01 00:00:00

  • Co-regulation of B-Myb expression by E2F1 and EGF receptor.

    abstract::Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is frequently over-expressed in human cancers and is associated with tumorigenesis, and increased tumor proliferation and progression. Also found in breast tumors with high levels is B-Myb, a transcription factor whose expression is activated b...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20147

    authors: Hanada N,Lo HW,Day CP,Pan Y,Nakajima Y,Hung MC

    更新日期:2006-01-01 00:00:00

  • Genetic variant rs16430 6bp > 0bp at the microRNA-binding site in TYMS and risk of sporadic breast cancer risk in non-Hispanic white women aged ≤ 55 years.

    abstract::Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in TYMS may alter cancer risk. In the study, we evaluated associations of three germline variants (rs2790 A > G, rs16430 6 bp > 0 bp, and rs1059394 C > T)...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22097

    authors: Guan X,Liu H,Ju J,Li Y,Li P,Wang LE,Brewster AM,Buchholz TA,Arun BK,Wei Q,Liu Z

    更新日期:2015-04-01 00:00:00

  • Phase II enzyme inducer, sulforaphane, inhibits UVB-induced AP-1 activation in human keratinocytes by a novel mechanism.

    abstract::Ultraviolet (UV) light-induced activation of activator protein-1 (AP-1), resulting at least in part from oxidative stress, promotes skin carcinogenesis. It has not yet been determined whether elevating cellular phase II enzymes and glutathione (GSH) levels inhibits the AP-1 activation. We have, therefore, examined the...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20052

    authors: Zhu M,Zhang Y,Cooper S,Sikorski E,Rohwer J,Bowden GT

    更新日期:2004-11-01 00:00:00