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EGF Receptor (D38B1) XP Rabbit mAb antibody


Antibody ID


Target Antigen

EGF Receptor See NCBI gene human, mouse, monkey

Proper Citation

(Cell Signaling Technology Cat# 4267, RRID:AB_2246311)


monoclonal antibody


Applications: W, IP, IHC-P, IF-IC, F. Consolidation: AB_10828841.

Clone ID


Host Organism


Radiologic and Genomic Evolution of Individual Metastases during HER2 Blockade in Colorectal Cancer.

  • Siravegna G
  • Cancer Cell
  • 2018 Jul 9

Literature context:


Targeting HER2 is effective in 24% of ERBB2 amplified metastatic colorectal cancer; however, secondary resistance occurs in most of the cases. We studied the evolution of individual metastases during treatment to discover spatially resolved determinants of resistance. Circulating tumor DNA (ctDNA) analysis identified alterations associated with resistance in the majority of refractory patients. ctDNA profiles and lesion-specific radiographic reports revealed organ- or metastasis-private evolutionary patterns. When radiologic assessments documented progressive disease in target lesions, response to HER2 blockade was retained in other metastases. Genomic and functional analyses on samples and cell models from eight metastases of a patient co-recruited to a postmortem study unveiled lesion-specific evolutionary trees and pharmacologic vulnerabilities. Lesion size and contribution of distinct metastases to plasma ctDNA were correlated.

Funding information:
  • NIEHS NIH HHS - ES06694(United States)

Liver Cancer Initiation Requires p53 Inhibition by CD44-Enhanced Growth Factor Signaling.

  • Dhar D
  • Cancer Cell
  • 2018 Jun 11

Literature context:


How fully differentiated cells that experience carcinogenic insults become proliferative cancer progenitors that acquire multiple initiating mutations is not clear. This question is of particular relevance to hepatocellular carcinoma (HCC), which arises from differentiated hepatocytes. Here we show that one solution to this problem is provided by CD44, a hyaluronic acid receptor whose expression is rapidly induced in carcinogen-exposed hepatocytes in a STAT3-dependent manner. Once expressed, CD44 potentiates AKT activation to induce the phosphorylation and nuclear translocation of Mdm2, which terminates the p53 genomic surveillance response. This allows DNA-damaged hepatocytes to escape p53-induced death and senescence and respond to proliferative signals that promote fixation of mutations and their transmission to daughter cells that go on to become HCC progenitors.

Funding information:
  • Intramural NIH HHS - Z01 ES101765(United States)
  • NCI NIH HHS - R01 CA118165()
  • NIEHS NIH HHS - P42 ES010337()

Angiogenin/Ribonuclease 5 Is an EGFR Ligand and a Serum Biomarker for Erlotinib Sensitivity in Pancreatic Cancer.

  • Wang YN
  • Cancer Cell
  • 2018 Apr 9

Literature context:


Pancreatic ribonuclease (RNase) is a secreted enzyme critical for host defense. We discover an intrinsic RNase function, serving as a ligand for epidermal growth factor receptor (EGFR), a member of receptor tyrosine kinase (RTK), in pancreatic ductal adenocarcinoma (PDAC). The closely related bovine RNase A and human RNase 5 (angiogenin [ANG]) can trigger oncogenic transformation independently of their catalytic activities via direct association with EGFR. Notably, high plasma ANG level in PDAC patients is positively associated with response to EGFR inhibitor erlotinib treatment. These results identify a role of ANG as a serum biomarker that may be used to stratify patients for EGFR-targeted therapies, and offer insights into the ligand-receptor relationship between RNase and RTK families.

Funding information:
  • NCI NIH HHS - P30 CA016672()
  • NCI NIH HHS - R01 CA211615()
  • NCI NIH HHS - T32 CA186892()
  • NCI NIH HHS - U01 CA201777()
  • NIGMS NIH HHS - R01 GM098294(United States)

Leptin suppresses adenosine triphosphate-induced impairment of spinal cord astrocytes.

  • Li B
  • J. Neurosci. Res.
  • 2017 Nov 3

Literature context:


Spinal cord injury (SCI) causes long-term disability and has no clinically effective treatment. After SCI, adenosine triphosphate (ATP) may be released from neuronal cells and astrocytes in large amounts. Our previous studies have shown that the extracellular release of ATP increases the phosphorylation of cytosolic phospholipase A2 (cPLA2 ) and triggers the rapid release of arachidonic acid (AA) and prostaglandin E2 (PGE2) via the stimulation of epidermal growth factor receptor (EGFR) and the downstream phosphorylation of extracellular-regulated protein kinases 1 and 2. Leptin, a glycoprotein, induces the activation of the Janus kinase (JAK2)/signal transducers and activators of transcription-3 (Stat3) pathway via the leptin receptor. In this study, we found that 1) prolonged leptin treatment suppressed the ATP-stimulated release of AA and PGE2 from cultured spinal cord astrocytes; 2) leptin elevated the expression of caveolin-1 (Cav-1) via the JAK2/Stat3 signaling pathway; 3) Cav-1 blocked the interaction between Src and EGFR, thereby inhibiting the phosphorylation of EGFR and cPLA2 and attenuating the release of AA or PGE2; 4) pretreatment with leptin decreased ;he level of apoptosis and the release of interleukin-6 from cocultured neurons and astrocytes; and 5) leptin improved the recovery of locomotion in mice after SCI. Our results highlight leptin as a promising therapeutic agent for SCI. © 2016 Wiley Periodicals, Inc.

Funding information:
  • NEI NIH HHS - R01 EY020533(United States)

PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K.

  • Malek M
  • Mol. Cell
  • 2017 Nov 2

Literature context:


The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P2. The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2, which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells. PTEN deletion increased PI(3,4)P2 levels in a mouse model of prostate cancer, and it inversely correlated with PI(3,4)P2 levels across several EGF-stimulated prostate and breast cancer lines. These results point to a role for PI(3,4)P2 in the phenotype caused by loss-of-function mutations or deletions in PTEN.

Funding information:
  • NINDS NIH HHS - R01 NS037462(United States)

Chemical Proteomics Identifies Druggable Vulnerabilities in a Genetically Defined Cancer.

  • Bar-Peled L
  • Cell
  • 2017 Oct 19

Literature context:


The transcription factor NRF2 is a master regulator of the cellular antioxidant response, and it is often genetically activated in non-small-cell lung cancers (NSCLCs) by, for instance, mutations in the negative regulator KEAP1. While direct pharmacological inhibition of NRF2 has proven challenging, its aberrant activation rewires biochemical networks in cancer cells that may create special vulnerabilities. Here, we use chemical proteomics to map druggable proteins that are selectively expressed in KEAP1-mutant NSCLC cells. Principal among these is NR0B1, an atypical orphan nuclear receptor that we show engages in a multimeric protein complex to regulate the transcriptional output of KEAP1-mutant NSCLC cells. We further identify small molecules that covalently target a conserved cysteine within the NR0B1 protein interaction domain, and we demonstrate that these compounds disrupt NR0B1 complexes and impair the anchorage-independent growth of KEAP1-mutant cancer cells. Our findings designate NR0B1 as a druggable transcriptional regulator that supports NRF2-dependent lung cancers.

EGFR Ligands Differentially Stabilize Receptor Dimers to Specify Signaling Kinetics.

  • Freed DM
  • Cell
  • 2017 Oct 19

Literature context:


Epidermal growth factor receptor (EGFR) regulates many crucial cellular programs, with seven different activating ligands shaping cell signaling in distinct ways. Using crystallography and other approaches, we show how the EGFR ligands epiregulin (EREG) and epigen (EPGN) stabilize different dimeric conformations of the EGFR extracellular region. As a consequence, EREG or EPGN induce less stable EGFR dimers than EGF-making them partial agonists of EGFR dimerization. Unexpectedly, this weakened dimerization elicits more sustained EGFR signaling than seen with EGF, provoking responses in breast cancer cells associated with differentiation rather than proliferation. Our results reveal how responses to different EGFR ligands are defined by receptor dimerization strength and signaling dynamics. These findings have broad implications for understanding receptor tyrosine kinase (RTK) signaling specificity. Our results also suggest parallels between partial and/or biased agonism in RTKs and G-protein-coupled receptors, as well as new therapeutic opportunities for correcting RTK signaling output.

Funding information:
  • NCI NIH HHS - P30 CA118100()
  • NCI NIH HHS - R01 CA112552()
  • NCI NIH HHS - R01 CA198164()
  • NCI NIH HHS - U54 CA193417()
  • NCI NIH HHS - U54 CA209992()
  • NIAID NIH HHS - AI061587(United States)
  • NIGMS NIH HHS - F32 GM109688()
  • NIGMS NIH HHS - P50 GM085273()
  • NIGMS NIH HHS - R01 GM099092()
  • NIGMS NIH HHS - R01 GM099321()
  • NIGMS NIH HHS - T32 GM008275()

Epidermal Growth Factor Receptor neddylation is regulated by a desmosomal-COP9 (Constitutive Photomorphogenesis 9) signalosome complex.

  • Najor NA
  • Elife
  • 2017 Sep 11

Literature context:


Cell junctions are scaffolds that integrate mechanical and chemical signaling. We previously showed that a desmosomal cadherin promotes keratinocyte differentiation in an adhesion-independent manner by dampening Epidermal Growth Factor Receptor (EGFR) activity. Here we identify a potential mechanism by which desmosomes assist the de-neddylating COP9 signalosome (CSN) in attenuating EGFR through an association between the Cops3 subunit of the CSN and desmosomal components, Desmoglein1 (Dsg1) and Desmoplakin (Dp), to promote epidermal differentiation. Silencing CSN or desmosome components shifts the balance of EGFR modifications from ubiquitination to neddylation, inhibiting EGFR dynamics in response to an acute ligand stimulus. A reciprocal relationship between loss of Dsg1 and neddylated EGFR was observed in a carcinoma model, consistent with a role in sustaining EGFR activity during tumor progression. Identification of this previously unrecognized function of the CSN in regulating EGFR neddylation has broad-reaching implications for understanding how homeostasis is achieved in regenerating epithelia.

Funding information:
  • NCI NIH HHS - P30 CA060553()
  • NCI NIH HHS - R01 CA122151()
  • NEI NIH HHS - EY020826(United States)
  • NIAMS NIH HHS - F32 AR066465()
  • NIAMS NIH HHS - P30 AR057216()
  • NIAMS NIH HHS - R01 AR041836()
  • NIAMS NIH HHS - R37 AR043380()
  • NIGMS NIH HHS - T32 GM008061()

EGFR Induces E2F1-Mediated Corticotroph Tumorigenesis.

  • Araki T
  • J Endocr Soc
  • 2017 Feb 1

Literature context:


The epidermal growth factor receptor (EGFR), expressed in adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas causing Cushing disease, regulates ACTH production and corticotroph proliferation. To elucidate the utility of EGFR as a therapeutic target for Cushing disease, we generated transgenic (Tg) mice with corticotroph-specific human EGFR expression (corti-EGFR-Tg) using a newly constructed corticotroph-specific promoter. Pituitary-specific EGFR expression was observed by 2.5 months, and aggressive ACTH-secreting pituitary adenomas with features of Crooke's cells developed by 8 months with 65% penetrance observed. Features consistent with the Cushing phenotype included elevated plasma ACTH and corticosterone levels, increased body weight, glucose intolerance, and enlarged adrenal cortex. Gefitinib, an EGFR tyrosine kinase inhibitor, suppressed tumor POMC expression and downstream EGFR tumor signaling, and ACTH and corticosterone levels were attenuated by 80% and 78%, respectively. Both E2F1 and phosphorylated Ser-337 E2F1 were increased in corti-EGFR-Tg mice and also colocalized with human POMC (hPOMC) in human pituitary corticotroph tumor samples. EGFR inhibition reversed E2F1 activity in vivo, whereas E2F1 inhibition suppressed POMC and ACTH in cultured human pituitary tumor cells. The corti-EGFR-Tg phenotype recapitulates ACTH-secreting pituitary adenomas and Cushing disease, validating the relevance of EGFR to corticotroph tumorigenesis. E2F1 is identified as a promising corticotroph-specific target for ACTH-dependent Cushing disease.

Funding information:
  • Canadian Institutes of Health Research - (Canada)

Crosstalk between CLCb/Dyn1-Mediated Adaptive Clathrin-Mediated Endocytosis and Epidermal Growth Factor Receptor Signaling Increases Metastasis.

  • Chen PH
  • Dev. Cell
  • 2017 Feb 6

Literature context:


Signaling receptors are internalized and regulated by clathrin-mediated endocytosis (CME). Two clathrin light chain isoforms, CLCa and CLCb, are integral components of the endocytic machinery whose differential functions remain unknown. We report that CLCb is specifically upregulated in non-small-cell lung cancer (NSCLC) cells and is associated with poor patient prognosis. Engineered single CLCb-expressing NSCLC cells, as well as "switched" cells that predominantly express CLCb, exhibit increased rates of CME and altered clathrin-coated pit dynamics. This "adaptive CME" resulted from upregulation of dynamin-1 (Dyn1) and its activation through a positive feedback loop involving enhanced epidermal growth factor (EGF)-dependent Akt/GSK3β phosphorylation. CLCb/Dyn1-dependent adaptive CME selectively altered EGF receptor trafficking, enhanced cell migration in vitro, and increased the metastatic efficiency of NSCLC cells in vivo. We define molecular mechanisms for adaptive CME in cancer cells and a role for the reciprocal crosstalk between signaling and CME in cancer progression.

Funding information:
  • NIGMS NIH HHS - R01 GM042455()
  • NIGMS NIH HHS - R01 GM073165()