A Novel EGFR Isoform Confers Increased Invasiveness to Cancer Cells

Zhou, Min; Wang, Hai; Zhou, Keke; Luo, Xiaoying; Pan, Xiaorong; Shi, Bizhi; Jiang, Hua; Zhang, Jiqin; Li, Kesang; Wang, Huamao; Gao, Huile; Lu, Shun; Yao, Ming; Mao, Ying; Wang, Hongyang; Yang, Shengli; Gu, Jianren; Li, Chuan-Yuan; Li, Zonghai

doi:10.1158/0008-5472.can-13-0194

Cited by 26 publications

(33 citation statements)

References 40 publications

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“…Structurally, EGFRvA is characterized by the substitution of exon 28 of EGFR with a serine/threonine-rich sequence [69]. Compared to wild-type EGFR, EGFRvA is more stable because of its decreased binding to c-Cbl [70], and it promotes cancer migration and invasion more significantly through activation of the STAT3 pathway and autocrine production of heparin-binding EGF [69].…”

Section: Splicing Of Egfr: An Alternative Methods To Control Tumourmentioning

confidence: 99%

“…Compared to wild-type EGFR, EGFRvA is more stable because of its decreased binding to c-Cbl [70], and it promotes cancer migration and invasion more significantly through activation of the STAT3 pathway and autocrine production of heparin-binding EGF [69]. EGFRvA is highly expressed in placenta and only slightly expressed in other normal tissues.…”

Section: Splicing Of Egfr: An Alternative Methods To Control Tumourmentioning

confidence: 99%

“…Many cancer cell lines and tissues have EGFRvA, suggesting a role in tumour development. The detection of EGFRvA is positively correlated with tumour grade and with adverse prognosis in glioma patients, more significantly than EGFR [69]. Thus, EGFRvA plays a critical role in the tumour progression of gliomas and might be a good therapeutic target for cancer treatment.…”

Section: Splicing Of Egfr: An Alternative Methods To Control Tumourmentioning

confidence: 99%

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Splice Variants of the RTK Family: Their Role in Tumour Progression and Response to Targeted Therapy

Abou-Faycal

Hatat

Gazzéri

et al. 2017

IJMS

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Receptor tyrosine kinases (RTKs) belong to a family of transmembrane receptors that display tyrosine kinase activity and trigger the activation of downstream signalling pathways mainly involved in cell proliferation and survival. RTK amplification or somatic mutations leading to their constitutive activation and oncogenic properties have been reported in various tumour types. Numerous RTK-targeted therapies have been developed to counteract this hyperactivation. Alternative splicing of pre-mRNA has recently emerged as an important contributor to cancer development and tumour maintenance. Interestingly, RTKs are alternatively spliced. However, the biological functions of RTK splice variants, as well as the upstream signals that control their expression in tumours, remain to be understood. More importantly, it remains to be determined whether, and how, these splicing events may affect the response of tumour cells to RTK-targeted therapies, and inversely, whether these therapies may impact these splicing events. In this review, we will discuss the role of alternative splicing of RTKs in tumour progression and response to therapies, with a special focus on two major RTKs that control proliferation, survival, and angiogenesis, namely, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-1 (VEGFR1).

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Section: Splicing Of Egfr: An Alternative Methods To Control Tumourmentioning

confidence: 99%

Section: Splicing Of Egfr: An Alternative Methods To Control Tumourmentioning

confidence: 99%

Section: Splicing Of Egfr: An Alternative Methods To Control Tumourmentioning

confidence: 99%

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Splice Variants of the RTK Family: Their Role in Tumour Progression and Response to Targeted Therapy

Abou-Faycal

Hatat

Gazzéri

et al. 2017

IJMS

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“…(Of note, however, is the recent observation that EGFR varieties are rarely coexpressed at the single cell level in GBM [24]. ) A newly identified EGFR variant, termed EGFRvA [91], also drives STAT3 activation, as does a reported EGFR-SEPT14 chimera [92]. …”

Section: Jak/stat3 In Gbmmentioning

confidence: 99%

NF-κB and STAT3 in glioblastoma: therapeutic targets coming of age

Gray¹,

McFarland²,

Nozell³

et al. 2014

Expert Review of Neurotherapeutics

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Since we last addressed the roles of NF-κB and JAK/STAT3 signaling in glioblastoma (GBM) five years ago, tremendous strides have been made in the understanding of these two pathways in glioma biology. Contributing to prosurvival mechanisms, cancer stem cell maintenance, and treatment resistance, both NF-κB and STAT3 have been characterized as major drivers of GBM. In this review, we address general improvements in the molecular understanding of GBM, the structure of NF-κB and STAT3 signaling, the ways in which these pathways contribute to GBM, and advances in preclinical and clinical targeting of these two signaling cascades.

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“…HB-EGF is known to activate STAT3 in glioma cells [20], and STAT3 is known to promote macrophage M2 polarization [21]. Based on these observations, we next tested whether the STAT3 pathway is involved in HB-EGF-induced macrophage M2 polarization.…”

Section: Resultsmentioning

confidence: 99%

M1 to M2 macrophage polarization in heparin-binding epidermal growth factor-like growth factor therapy for necrotizing enterocolitis

Wei

Besner

2015

Journal of Surgical Research

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Background Macrophages can be polarized into pro-inflammatory (M1) and anti-inflammatory (M2) subtypes. However, whether macrophage polarization plays a role in necrotizing enterocolitis (NEC) remains unknown. Materials and methods Macrophages were derived from the THP-1 human monocyte cell line. Apoptosis of human fetal small intestinal epithelial FHs-74 cells was determined by Annexin V/PI flow cytometry and by Western blotting to detect cleaved caspase-3. The effect of heparin-binding EGF-like growth factor (HB-EGF) on macrophage polarization was determined by flow cytometry with M1/ M2 markers and real time PCR. In vivo, experimental NEC was induced in mouse pups by repeated exposure to hypoxia, hypothermia and hypertonic feedings. Intestinal histologic sections were subjected to immunohistochemical staining for the detection of M1 and M2 macrophages. Results In vitro, FHs-74 cell apoptosis was increased after co-culture with macrophages and LPS. This apoptosis was increased by exposure to M1 conditioned medium (CM) and suppressed by exposure to M2 CM. HB-EGF significantly decreased LPS-induced M1 polarization and promoted M2 polarization via STAT3 activation. Addition of HB-EGF to LPS-stimulated macrophages suppressed the pro-apoptotic effects of the macrophages on FHs-74 cells. In vivo, we found enhanced intestinal macrophage infiltration in pups subjected to NEC, the majority of which were M1 macrophages. HB-EGF treatment of pups subjected to experimental NEC significantly reduced M1 and increased M2 polarization, and protected the intestines from NEC. Conclusions M1 macrophages promote NEC by increasing intestinal epithelial apoptosis. HB-EGF protects the intestines from NEC by preventing M1 and promoting M2 polarization.

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A Novel EGFR Isoform Confers Increased Invasiveness to Cancer Cells

Cited by 26 publications

References 40 publications

Splice Variants of the RTK Family: Their Role in Tumour Progression and Response to Targeted Therapy

Splice Variants of the RTK Family: Their Role in Tumour Progression and Response to Targeted Therapy

NF-κB and STAT3 in glioblastoma: therapeutic targets coming of age

M1 to M2 macrophage polarization in heparin-binding epidermal growth factor-like growth factor therapy for necrotizing enterocolitis

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