EGFR and KRAS in Colorectal Cancer

Markman, Ben; Ramos, Francisco Javier; Capdevila, Jaume; Tabernero, Josep

doi:10.1016/s0065-2423(10)51004-7

Cited by 110 publications

(77 citation statements)

References 95 publications

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“…Together, these results indicate that concurrent upregulation of the growth factor and non-canonical Wnt pathways spurred by Daple is associated with poorer clinical outcomes. Findings are in keeping with a working model (see legend Fig 6F) in which G protein signaling via Daple can be triggered by both growth factor and non-canonical Wnt cascades, two pathways that are frequently upregulated during oncogenic progression and are known to promote tumor cell dissemination (28, 46). …”

Section: Resultssupporting

confidence: 85%

Convergence of Wnt, growth factor, and heterotrimeric G protein signals on the guanine nucleotide exchange factor Daple

et al. 2018

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Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades; their concurrent dysregulation plays an integral role in cancer progression and is a common feature of many malignancies. Three such cascades that contribute to the oncogenic potential are those mediated by Wnt and Frizzled (FZD), growth factor receptor tyrosine kinases (RTKs), and trimeric G proteins and GPCRs. Daple is a Dishevelled (Dvl)- and FZD-binding protein and a guanine-nucleotide exchange factor (GEF) for the trimeric G protein, Gαi. Daple enhances β-catenin-independent Wnt signaling through its ability to activate the pathway downstream of the Wnt5/FZD7 pathway. Here we identified that Daple is a substrate of multiple RTKs and non-RTKs, and hence, a point of convergence for all three cascades. We show that phosphorylation by both RTKs and non-RTKs near the Dvl-binding motif in Daple dissociated Daple:Dvl complexes and augmented the ability of Daple to bind and activate Gαi which potentiated β-catenin-independent Wnt signals and triggered epithelial-mesenchymal transition (EMT) in a manner similar to that triggered by Wnt5A/FZD. Although Daple acts as a tumor suppressor in the healthy colon, but concurrent upregulation of Daple and epidermal growth factor receptor (EGFR) in colorectal tumors from patients was associated with poor prognosis. We conclude that Daple-dependent activation of Gαi and enhancement of β-catenin-independent Wnt signals is not just triggered by Wnt5a/FZD to suppress tumorigenesis, but also is hijacked by growth factor-RTKs to stoke tumor progression. Thus, this work defines a crosstalk paradigm amongst growth factor RTKs, trimeric G-proteins, and Wnt/FZD in cancer biology.

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Section: Resultssupporting

confidence: 85%

Convergence of Wnt, growth factor, and heterotrimeric G protein signals on the guanine nucleotide exchange factor Daple

et al. 2018

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“…It is well known that tumor immunotherapy is to eliminate tumor cells by activating immune system, while EBV-associated NPC traditional immunotherapy is based on the function of autologous CTL activity (Chua et al, 2001;Leen et al, 2009). On the other hand, B cell mediated humoral immune response also plays an indispensable role, such as neutralization, opsonization and ADCC effects (Chao et al, 2010;Rhodes et al, 2010;Markman et al, 2010). So it would be a good approach to improve the efficacy of a candidate therapeutic vaccine to induce specific cellular and humoral immune coresponse against EBV associated malignancies.…”

Section: Discussionmentioning

confidence: 99%

Immune response of mice to a latency membrane protein 2 multiepitope antigen of Epstein-Barr virus applied as DNA vaccine and/or peptide vaccine

Li¹,

Q²,

Chen³

et al. 2013

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Summary. -To evaluate immune responses of mice to a latent membrane protein 2 (LMP2) multiepitope antigen of Epstein-Barr virus (EBV), four kinds of prime-boost strategies were applied. In group 1, mice were primed and boosted with DNA vaccine delivered by human papillomavirus (HPV) major capsid protein L1 on weeks 0, 2, 4, and 6. Mice in group 2 were primed with DNA vaccine on weeks 0 and 2, and boosted with peptide vaccine on weeks 4 and 6. In group 3, mice were primed with peptide vaccine on weeks 0 and 2, and boosted with DNA vaccine on weeks 4 and 6. Mice in group 4 were primed and boosted with DNA vaccine together with peptide vaccine on weeks 0, 2, 4 and 6. EBV-LMP2-specific IgG, IgG1, IgG2a, and IgA antibodies, and HPV L1-specific IgG antibodies were determined by ELISA. Cytotoxic T-lymphocytes (CTL) activity was measured by LDH release assay. The results of this study show that priming with DNA vaccine, and boosting with peptide vaccine (group 2) induced a significant humoral immune response, and also an effective CTL activity, which could be regarded as an optimal prime-boost strategy for improving the immune effects of EBV-LMP2 multiepitope antigen.Keywords: human papillomavirus 6; major capsid protein L1; Epstein-Barr virus; latent membrane protein 2; multiepitope antigen; virus-like particles; DNA vaccine; peptide vaccine; prime-boost strategy * Corresponding author. E-mail: lifangzhang@126.com; phone: +86-577-86689910. Abbreviations: CTL = cytotoxic T lymphocytes; EBV = EpsteinBarr virus; E:T = effector/target cells ratio; HPV = human papillomavirus; LMP2 = latent membrane protein 2; NPC = nasopharyngeal carcinoma; VLPs = virus-like particles

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“…These oligonucleotides are complimentary to genes on the array and allow the measurement of particular gene expression profiles with high sensitivity. This array is unable to predict and analyze unknown genes, as their sequences need to be known for the manufacture of the [219] PSA [220] Cyclooxygenasearachidonic acid metabolites [221] 2000 cell surface protein cluster in cancer [222] Ovarian BRCA1 BRCA2 mutations [223] CpG-island hypermethylation (BRCA1) [224] Prostasin [225] HE4 [226] Ca125 [227] Eosinophil-derived neurotoxin and COOHterminal osteopontin [228] Breast BRCA1 BRCA2 mutations [223] CpG-island hypermethylation (BRCA1, E-cadherin, TMS1 and estrogen receptor) [229] EpCAM, CD45 [230] Pancreatic Palladin mutation [231] BNC1 ADAMTS1 methylation [232] A1-antitrypsin Apolipoprotein A1 [233] Gastric PTEN mutation [234] CpG-island hypermethylation (hMLH1 and p14ARF) [235] miR-1, miR20a, miR-27a, miR-34 and miR-423-5p expression [236] Hepatocellular RASSF1A, SSBP2 and B4GALT1 hypermethylation [237] AFP-L3 [238] Colorectal CpG-island hypermethylation, hypermethylation of miRNAs (miR-124a) [239] p53 expression [239], EGFR-related KRAS [240], c-MET, b-catenin [241] CEA [242] Smaller number of combinational molecular phenotype cluster in cancer [167] Some of these biomarkers are currently in clinical practice. AFP: Alpha feto-protein; CEA: Carcino-embryonic antigen; PSA: Prostate specific antigen.…”

Section: Genomicsmentioning

confidence: 99%

Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology

Theophilou

Paraskevaidi

Lima

et al. 2015

Expert Review of Molecular Diagnostics

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The complex processes driving cancer have so far impeded the discovery of dichotomous biomarkers associated with its initiation and progression. Reductionist approaches utilizing 'omics' technologies have met some success in identifying molecular alterations associated with carcinogenesis. Systems biology is an emerging science that combines high-throughput investigation techniques to define the dynamic interplay between regulatory biological systems in response to internal and external cues. Vibrational spectroscopy has the potential to play an integral role within systems biology research approaches. It is capable of examining global models of carcinogenesis by scrutinizing chemical bond alterations within molecules. The application of infrared or Raman spectroscopic approaches coupled with computational analysis under the systems biology umbrella can assist the transition of biomarker research from the molecular level to the system level. The comprehensive representation of carcinogenesis as a multilevel biological process will inevitably revolutionize cancer-related healthcare by personalizing risk prediction and prevention.

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EGFR and KRAS in Colorectal Cancer

Cited by 110 publications

References 95 publications

Convergence of Wnt, growth factor, and heterotrimeric G protein signals on the guanine nucleotide exchange factor Daple

Convergence of Wnt, growth factor, and heterotrimeric G protein signals on the guanine nucleotide exchange factor Daple

Immune response of mice to a latency membrane protein 2 multiepitope antigen of Epstein-Barr virus applied as DNA vaccine and/or peptide vaccine

Extracting biomarkers of commitment to cancer development: potential role of vibrational spectroscopy in systems biology

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