Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR and affects clinical outcomes of patients.

Abstract:

:Tyrosine kinase inhibitor (TKI)-sensitive and TKI-resistant mutations of epidermal growth factor receptor (EGFR) are associated with lung adenocarcinoma. EGFR mutants were previously shown to exhibit ligand-independent activation. We have previously demonstrated that pulmonary surfactant protein D (SP-D, SFTPD) suppressed wild-type EGFR signaling by blocking ligand binding to EGFR. We herein demonstrate that SFTPD downregulates ligand-independent signaling in cells harboring EGFR mutations such as TKI-sensitive exon 19 deletion (Ex19del) and L858R mutation as well as TKI-resistant T790M mutation, subsequently suppressing cellular growth and motility. Lectin blotting and ligand blotting in lung cancer cell lines suggested that EGFR mutants express oligomannose-type N-glycans and interact with SFTPD directly. Cross-linking assay indicated that SFTPD inhibits ligand-independent dimerization of EGFR mutants. We also demonstrated that SFTPD reduced dimerization-independent phosphorylation of Ex19del and T790M EGFR mutants using point mutations that disrupted the asymmetric dimer interface. It was confirmed that SFTPD augmented the viability-suppressing effects of EGFR-TKIs. Furthermore, retrospective analysis of 121 patients with lung adenocarcinoma to examine associations between serum SFTPD levels and clinical outcome indicated that in TKI-treated patients with lung cancer harboring EGFR mutations, including Ex19del or L858R, high serum SFTPD levels correlated with a lower number of distant metastases and prolonged overall survival and progression-free survival. These findings suggest that SFTPD downregulates both TKI-sensitive and -resistant EGFR mutant signaling, and SFTPD level is correlated with clinical outcome. These findings illustrate the use of serum SFTPD level as a potential marker to estimate the efficacy of EGFR-TKIs.

journal_name

Oncogene

journal_title

Oncogene

authors

Umeda Y,Hasegawa Y,Otsuka M,Ariki S,Takamiya R,Saito A,Uehara Y,Saijo H,Kuronuma K,Chiba H,Ohnishi H,Sakuma Y,Takahashi H,Kuroki Y,Takahashi M

doi

10.1038/onc.2017.253

subject

Has Abstract

pub_date

2017-11-16 00:00:00

pages

6432-6445

issue

46

eissn

0950-9232

issn

1476-5594

pii

onc2017253

journal_volume

36

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Signal transduction pathways regulated by arsenate and arsenite.

    abstract::Arsenate and arsenite activate c-Jun N-terminal kinase (JNK), however, the mechanism by which this occurs is not known. By expressing inhibitory mutant small GTP-binding proteins, p21-activated kinase (PAK) and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinases (MEKKs), we have ident...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203214

    authors: Porter AC,Fanger GR,Vaillancourt RR

    更新日期:1999-12-16 00:00:00

  • MSX2 is an oncogenic downstream target of activated WNT signaling in ovarian endometrioid adenocarcinoma.

    abstract::Ovarian endometrioid adenocarcinomas (OEAs) frequently exhibit constitutive activation of canonical WNT signaling, usually as a result of oncogenic mutations that stabilize and dysregulate the β-catenin protein. In previous work, we used microarray-based methods to compare gene expression in OEAs with and without dysr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.123

    authors: Zhai Y,Iura A,Yeasmin S,Wiese AB,Wu R,Feng Y,Fearon ER,Cho KR

    更新日期:2011-10-06 00:00:00

  • Silencing of the Tropomyosin-1 gene by DNA methylation alters tumor suppressor function of TGF-beta.

    abstract::Loss of actin stress fibers has been associated with cell transformation and metastasis. TGF-beta induction of stress fibers in epithelial cells requires high molecular weight tropomyosins encoded by TPM1 and TPM2 genes. Here, we investigated the mechanism underlying the failure of TGF-beta to induce stress fibers and...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208688

    authors: Varga AE,Stourman NV,Zheng Q,Safina AF,Quan L,Li X,Sossey-Alaoui K,Bakin AV

    更新日期:2005-07-28 00:00:00

  • Nrh, a human homologue of Nr-13 associates with Bcl-Xs and is an inhibitor of apoptosis.

    abstract::In search of human homologues of the anti-apoptotic protein Nr-13, we have characterized a human EST clone that potentially encodes a protein, which is the closest homologue of Nr-13 among the Bcl-2 family members, to date known, in humans. Phylogenetic analyses suggest Human nrh, Mouse diva/boo and Quail nr-13 to be ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204740

    authors: Aouacheria A,Arnaud E,Venet S,Lalle P,Gouy M,Rigal D,Gillet G

    更新日期:2001-09-13 00:00:00

  • TRIM24 links glucose metabolism with transformation of human mammary epithelial cells.

    abstract::Tripartite motif 24 protein (TRIM24) is a plant homeodomain/bromodomain histone reader, recently associated with poor overall survival of breast-cancer patients. At a molecular level, TRIM24 is a negative regulator of p53 levels and a co-activator of estrogen receptor. However, the role of TRIM24 in breast tumorigenes...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.220

    authors: Pathiraja TN,Thakkar KN,Jiang S,Stratton S,Liu Z,Gagea M,Shi X,Shah PK,Phan L,Lee MH,Andersen J,Stampfer M,Barton MC

    更新日期:2015-05-28 00:00:00

  • Apoptosis signaling triggered by the marine alkaloid ascididemin is routed via caspase-2 and JNK to mitochondria.

    abstract::The marine alkaloid ascididemin (ASC) was shown to exert cytotoxicity even against multidrug-resistant cancer cells. Here, we address the signaling pathways utilized by ASC to trigger apoptosis in Jurkat leukemia T cells. We show that ASC (0.5-20 microM) induces a mitochondrial pathway that requires the activation of ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207281

    authors: Dirsch VM,Kirschke SO,Estermeier M,Steffan B,Vollmar AM

    更新日期:2004-02-26 00:00:00

  • Complex regulation of human androgen receptor expression by Wnt signaling in prostate cancer cells.

    abstract::beta-Catenin, a component of the Wnt signaling pathway, is a coactivator of human androgen receptor (hAR) transcriptional activity. Here, we show that Wnt signaling also influences androgen-mediated signaling through its ability to regulate hAR mRNA and protein in prostate cancer (PCa) cells. Three functional LEF-1/TC...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209366

    authors: Yang X,Chen MW,Terry S,Vacherot F,Bemis DL,Capodice J,Kitajewski J,de la Taille A,Benson MC,Guo Y,Buttyan R

    更新日期:2006-06-08 00:00:00

  • Poly(ADP-ribosyl)ation of p53 induces gene-specific transcriptional repression of MTA1.

    abstract::The metastasis-associated protein 1 (MTA1) is overexpressed in various human cancers and is closely connected with aggressive phenotypes; however, little is known about the transcriptional regulation of the MTA1 gene. This study identified the MTA1 gene as a target of p53-mediated transrepression. The MTA1 promoter co...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.2

    authors: Lee MH,Na H,Kim EJ,Lee HW,Lee MO

    更新日期:2012-12-06 00:00:00

  • Ras controls coupling of growth factor receptors and protein kinase C in the membrane to Raf-1 and B-Raf protein serine kinases in the cytosol.

    abstract::A dominant negative mutant of Ras, M17 Ras, was used to study the role of Ras in receptor coupling of Raf-1 and B-Raf protein serine/threonine kinases (PSKs). We found that mutant Ras blocks serum- and 12-O-tetradecanoyl phorbol 13-acetate-induced activation of Raf-1 kinase in NIH3T3 cells and Raf-1 as well as B-Raf P...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Troppmair J,Bruder JT,App H,Cai H,Liptak L,Szeberényi J,Cooper GM,Rapp UR

    更新日期:1992-09-01 00:00:00

  • Regulation of SV40 large T-antigen stability by reversible acetylation.

    abstract::Reversible acetylation on protein lysine residues has been shown to regulate the function of both nuclear proteins such as histones and p53 and cytoplasmic proteins such as alpha-tubulin. To identify novel acetylated proteins, we purified several proteins by the affinity to an anti-acetylated-lysine antibody from cell...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209731

    authors: Shimazu T,Komatsu Y,Nakayama KI,Fukazawa H,Horinouchi S,Yoshida M

    更新日期:2006-11-30 00:00:00

  • A 19S proteasomal subunit cooperates with an ERK MAPK-regulated degron to regulate accumulation of Fra-1 in tumour cells.

    abstract::Fos-related antigen-1 (Fra-1) is a member of the Activator Protein-1 (AP-1) transcription factor superfamily that is overexpressed in a variety of cancers, including colon, breast, lung, bladder and brain. High Fra-1 levels are associated with enhanced cell proliferation, survival, migration and invasion. Despite its ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.375

    authors: Pakay JL,Diesch J,Gilan O,Yip YY,Sayan E,Kolch W,Mariadason JM,Hannan RD,Tulchinsky E,Dhillon AS

    更新日期:2012-04-05 00:00:00

  • Protein interactions at Sp1-like sites in the TGF alpha promoter as visualized by in vivo genomic footprinting.

    abstract::Transcription from the rat TGF alpha promoter initiates at two predominant sites (-188 and -58) in a G+C-rich region that does not contain TATA or CAAT motifs. Previous studies using transfected reporter constructs implicated the transcription factor Sp1 in active expression from the promoter, particularly from the -5...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Chen X,Wright KL,Berkowitz EA,Azizkhan JC,Ting JP,Lee DC

    更新日期:1994-11-01 00:00:00

  • PIKE-A is a proto-oncogene promoting cell growth, transformation and invasion.

    abstract::PIKE-A (phosphoinositide 3-kinases (PI 3)-kinase enhancer) is a ubiquitously expressed GTPase, which binds to and enhances protein kinase B (Akt) kinase activity in a guanine nucleotide-dependent manner. PIKE-A is one of the components of the CDK4 amplicon that is amplified in numerous human cancers. However, whether ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210290

    authors: Liu X,Hu Y,Hao C,Rempel SA,Ye K

    更新日期:2007-07-26 00:00:00

  • The RON receptor tyrosine kinase promotes MSP-independent cell spreading and survival in breast epithelial cells.

    abstract::The recepteur d'origine nantais (RON) is a receptor tyrosine kinase (RTK) in the scatter factor family, which includes the c-Met receptor. RON exhibits increased expression in a significant number of human breast cancer tissues as well as in many established breast cancer cell lines. Recent studies have indicated that...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.383

    authors: Feres KJ,Ischenko I,Hayman MJ

    更新日期:2009-01-15 00:00:00

  • Epigenetic patterns of the retinoic acid receptor beta2 promoter in retinoic acid-resistant thyroid cancer cells.

    abstract::Treatment with retinoic acid (RA) is effective to restore radioactive iodine uptake in metastases of a small fraction of thyroid cancer patients. In order to find predictive markers of response, we took advantage of two thyroid cancer cell lines, FTC133 and FTC238, with low RA-receptor (RAR)beta expression but differi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210178

    authors: Cras A,Darsin-Bettinger D,Balitrand N,Cassinat B,Soulié A,Toubert ME,Delva L,Chomienne C

    更新日期:2007-06-07 00:00:00

  • Caspase-dependent processing activates the proapoptotic activity of deleted in breast cancer-1 during tumor necrosis factor-alpha-mediated death signaling.

    abstract::Deleted in breast cancer-1 (DBC-1) was initially cloned from a homozygously deleted region in breast and other cancers on human chromosome 8p21, although no function is known for the protein product it encodes. We identified the generation of amino-terminally truncated versions of DBC-1 during tumor necrosis factor (T...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208681

    authors: Sundararajan R,Chen G,Mukherjee C,White E

    更新日期:2005-07-21 00:00:00

  • Dinucleotide repeats negatively modulate the promoter activity of Cyr61 and is unstable in hepatocellular carcinoma patients.

    abstract::Cyr61 is a secreted, cysteine-rich, heparin-binding protein that mediates diverse functions including extracellular matrix formation, differentiation, cell proliferation, adhesion, migration, survival, as well as angiogenesis and tumorigenesis. In this study, we found that Cyr61 gene expression is significantly downre...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208550

    authors: Wang B,Ren J,Ooi LL,Chong SS,Lee CG

    更新日期:2005-06-02 00:00:00

  • Identification of multiple SNT-binding sites on NPM-ALK oncoprotein and their involvement in cell transformation.

    abstract::The t(2;5) chromosomal translocation occurs in anaplastic large-cell lymphoma arising from activated T lymphocytes. This genomic rearrangement generates the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) oncoprotein that is a chimeric protein consisting of parts of the nuclear protein NPM and ALK receptor protei...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210095

    authors: Chikamori M,Fujimoto J,Tokai-Nishizumi N,Yamamoto T

    更新日期:2007-05-03 00:00:00

  • The oncogene PDGF-B provides a key switch from cell death to survival induced by TNF.

    abstract::Tumor necrosis factor (TNF) induces both cell death and survival signals. NF-kappaB, a transcription factor activated by TNF, is critical for controlling survival signals through trans-activation of downstream target genes. However, few NF-kappaB target survival genes have been identified with direct roles in oncogene...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208516

    authors: Au PY,Martin N,Chau H,Moemeni B,Chia M,Liu FF,Minden M,Yeh WC

    更新日期:2005-04-28 00:00:00

  • Progesterone enhances branching morphogenesis in the mouse mammary gland by increased expression of Msx2.

    abstract::Branching morphogenesis within the peripubertal mouse mammary gland is directed by progesterone (P). A role for the homeobox-containing transcription factor, Msx2, during branching morphogenesis is suggested from its ontogenic expression profile and hormonal regulation. Herein, we define the spatio-temporal control of...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210555

    authors: Satoh K,Hovey RC,Malewski T,Warri A,Goldhar AS,Ginsburg E,Saito K,Lydon JP,Vonderhaar BK

    更新日期:2007-11-29 00:00:00

  • Activation-dependent degradation of protein kinase C eta.

    abstract::Prolonged activation of protein kinase Cs (PKCs) by long-term treatment of cells with phorbol ester tumor promoters down-regulates the expression of many PKCs. To investigate the molecular mechanisms involved in the down-regulation of PKC eta, we expressed the novel PKCs eta and θ and various mutant forms in bab...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203779

    authors: Kang BS,French OG,Sando JJ,Hahn CS

    更新日期:2000-08-31 00:00:00

  • Mapping of MAX to human chromosome 14 and mouse chromosome 12 by in situ hybridization.

    abstract::The protein encoded by the MAX gene is a member of the class of basic region-helix-loop-helix-zipper proteins and has been demonstrated to associate with N-, L-, and c-Myc proteins both in vitro and in vivo. Heterodimers formed between c-Myc and Max proteins have been shown to possess sequence-specific DNA-binding act...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Gilladoga AD,Edelhoff S,Blackwood EM,Eisenman RN,Disteche CM

    更新日期:1992-06-01 00:00:00

  • Constitutive DNA damage is linked to DNA replication abnormalities in Bloom's syndrome cells.

    abstract::Bloom's syndrome (BS) is an autosomal recessive disorder associated with an elevated incidence of cancers. The gene mutated in BS, BLM, encodes a RecQ helicase family member. BS cells exhibit genomic instability, including excessive homologous recombination and chromosomal aberrations. We reported previously that BS c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206970

    authors: Rassool FV,North PS,Mufti GJ,Hickson ID

    更新日期:2003-11-27 00:00:00

  • The β-catenin/TCF-4-LINC01278-miR-1258-Smad2/3 axis promotes hepatocellular carcinoma metastasis.

    abstract::Hepatocellular carcinoma (HCC) metastasis is largely responsible for HCC-associated recurrence and mortality. We aimed to identify metastasis-related long non-coding RNAs (lncRNAs) to understand the molecular mechanism of HCC metastasis. We first identified that miR-1258 was downregulated in HCC tissues both in The Ca...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-1307-3

    authors: Huang WJ,Tian XP,Bi SX,Zhang SR,He TS,Song LY,Yun JP,Zhou ZG,Yu RM,Li M

    更新日期:2020-06-01 00:00:00

  • Identification of expressed genes characterizing long-term survival in malignant glioma patients.

    abstract::Better understanding of the underlying biology of malignant gliomas is critical for the development of early detection strategies and new therapeutics. This study aimed to define genes associated with survival. We investigated whether genes coupled with a class prediction model could be used to define subgroups of hig...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209585

    authors: Yamanaka R,Arao T,Yajima N,Tsuchiya N,Homma J,Tanaka R,Sano M,Oide A,Sekijima M,Nishio K

    更新日期:2006-09-28 00:00:00

  • MET targeting: time for a rematch.

    abstract::MET, the receptor tyrosine kinase (RTK) for hepatocyte growth factor, is a proto-oncogene involved in embryonic development and throughout life in homeostasis and tissue regeneration. Deregulation of MET signaling has been reported in numerous malignancies, prompting great interest in MET targeting for cancer therapy....

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/s41388-020-1193-8

    authors: Koch JP,Aebersold DM,Zimmer Y,Medová M

    更新日期:2020-04-01 00:00:00

  • Association of extended in vitro proliferative potential with loss of p16INK4 expression.

    abstract::This study addresses the question of whether loss of p16INK4 expression contributes to the immortalization of human cells. In vitro immortalization usually proceeds through two phases. In the first phase (lifespan extension), cells continue proliferating and their telomeres continue shortening beyond the point at whic...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Noble JR,Rogan EM,Neumann AA,Maclean K,Bryan TM,Reddel RR

    更新日期:1996-09-19 00:00:00

  • Intermediate filament dynamics and breast cancer: aberrant promoter methylation of the Synemin gene is associated with early tumor relapse.

    abstract::Synemin (SYNM) is a type IV intermediate filament that has recently been shown to interact with the LIM domain protein zyxin, thereby possibly modulating cell adhesion and cell motility. Owing to this multiplicity of potential functions relevant to cancer development, we initiated a study to decipher SYNM expression a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.229

    authors: Noetzel E,Rose M,Sevinc E,Hilgers RD,Hartmann A,Naami A,Knüchel R,Dahl E

    更新日期:2010-08-26 00:00:00

  • JunD activates transcription of the human ferritin H gene through an antioxidant response element during oxidative stress.

    abstract::Ferritin is the major intracellular iron storage protein that sequesters excess free iron to minimize generation of iron-catalysed reactive oxygen species. We previously demonstrated that expression of ferritin heavy chain (ferritin H) was induced by pro-oxidants, which is a part of cellular antioxidant response to pr...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208901

    authors: Tsuji Y

    更新日期:2005-11-17 00:00:00

  • Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays.

    abstract::Identifying novel and known genes that are differentially expressed in breast cancer has important implications in understanding the biology of breast tumorigenesis and developing new diagnostic and therapeutic agents. In this study we have combined two powerful technologies, PCR-based cDNA subtraction and cDNA microa...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205278

    authors: Jiang Y,Harlocker SL,Molesh DA,Dillon DC,Stolk JA,Houghton RL,Repasky EA,Badaro R,Reed SG,Xu J

    更新日期:2002-03-28 00:00:00