Constitutively Active Type I Insulin-Like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and Is Accompanied by an Epithelial-to-Mesenchymal Transition Mediated by NF-κB and Snail

Kim, Hyun Jung; Litzenburger, Beate C.; Cui, Xiaojiang; Delgado, David A.; Grabiner, Brian C.; Lin, Xin; Lewis, Michael T.; Gottardis, Marco M.; Wong, Tai W.; Attar, Ricardo M.; Carboni, Joan M.; Lee, Adrian V.

doi:10.1128/mcb.01315-06

Cited by 217 publications

(177 citation statements)

References 53 publications

Supporting

Mentioning

172

Contrasting

Unclassified

Order By: Relevance

“…IFG1 is known to increase breast cancer development and breast cancer recurrence (Kim et al 2007, Smith et al 2011. In the normal breast, the IGF1 pathway is known to be critical for mammary gland development and progesterone Gene set enrichment analysis (GSEA) showing high expression of the G protein-coupled receptor pathway and the serotonin receptor pathway in patients diagnosed with breast cancer during pregnancy (both P values after correction for multiple testing; FDR !0.0001).…”

Section: Discussionmentioning

confidence: 99%

Biology of breast cancer during pregnancy using genomic profiling

Azim

Brohée

Peccatori

et al. 2014

Endocrine Related Cancer

View full text Add to dashboard Cite

Breast cancer during pregnancy is rare and is associated with relatively poor prognosis. No information is available on its biological features at the genomic level. Using a dataset of 54 pregnant and 113 non-pregnant breast cancer patients, we evaluated the pattern of hot spot somatic mutations and did transcriptomic profiling using Sequenom and Affymetrix respectively. We performed gene set enrichment analysis to evaluate the pathways associated with diagnosis during pregnancy. We also evaluated the expression of selected cancer-related genes in pregnant and non-pregnant patients and correlated the results with changes occurring in the normal breast using a pregnant murine model. We finally investigated aberrations associated with disease-free survival (DFS). No significant differences in mutations were observed. Of the total number of patients, 18.6% of pregnant and 23% of non-pregnant patients had a PIK3CA mutation. Around 30% of tumors were basal, with no differences in the distribution of breast cancer molecular subtypes between pregnant and non-pregnant patients. Two pathways were enriched in tumors diagnosed during pregnancy: the G protein-coupled receptor pathway and the serotonin receptor pathway (FDR !0.0001). Tumors diagnosed during pregnancy had higher expression of PD1 (PDCD1; PZ0.015), PDL1 (CD274; PZ0.014), and gene sets related to SRC (PZ0.004), IGF1 (PZ0.032), and b-catenin (PZ0.019). Their expression increased almost linearly throughout gestation when evaluated on the normal breast using a pregnant mouse model underscoring the potential effect of the

show abstract

Section: Discussionmentioning

confidence: 99%

Biology of breast cancer during pregnancy using genomic profiling

Azim

Brohée

Peccatori

et al. 2014

Endocrine Related Cancer

View full text Add to dashboard Cite

show abstract

“…In PC9 NSCLC cells made erlotinib-resistant in vitro, EMT was reversed upon IGF1R inhibition with I-OMe-AG538 indicating a role for IGF1R in TKI resistance related EMT (53). A study on IGF1R overexpressing cells highlighted the EMT transcription factor SNAIL as the downstream effector of IGF1R-induced EMT (66). Our own studies (unpublished results) and studies from others suggest a role for IGF1R in EMT initiation, but also that established mesenchymal-like lung adenocarcinoma cells no longer depended on IGF1R signaling for proliferation or survival (67).…”

Section: Igf1rmentioning

confidence: 99%

The role of epithelial to mesenchymal transition in resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer

Jakobsen

Demuth

Sørensen³

et al. 2016

Transl. Lung Cancer Res.

View full text Add to dashboard Cite

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and resistance to lung cancer therapy Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death worldwide. The 5-year survival remains at 10-15% despite advances in treatment options.Erlotinib, a TKI targeting EGFR, was initially explored as a second-line treatment in NSCLC patients progressing on standard chemotherapy. Survival was prolonged compared to placebo (1). However, erlotinib was soon discovered to be especially efficient in patients with a mutation in the tyrosine kinase domain of EGFR. These patients are nowThe role of epithelial to mesenchymal transition in resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer Correspondence to: Anders Lade Nielsen. Department of Biomedicine, Bartholin Building, Aarhus University, DK-8000, Aarhus C, Denmark.Email: aln@biomed.au.dk.Abstract: Inhibition of the epidermal growth factor receptor (EGFR) is an important strategy when treating non-small cell lung cancer (NSCLC) patients. However, intrinsic resistance or development of resistance during the course of treatment constitutes a major challenge. The knowledge on EGFRdirected tyrosine kinase inhibitors (TKIs) and their biological effect keeps increasing. Within the group of patients with EGFR mutations some benefit to a much higher degree than others, and for patients lacking EGFR mutations a subset experience an effect. Up to 70% of patients with EGFR mutations and 10-20% of patients without EGFR mutations initially respond to the EGFR-TKI erlotinib, but there is a severe absence of good prognostic markers. Despite initial effect, all patients acquire resistance to EGFR-TKIs.Multiple mechanisms have implications in resistance development, but much is still to be explored. Epithelial to mesenchymal transition (EMT) is a transcriptionally regulated phenotypic shift rendering cells more invasive and migratory. Within the EMT process lays a need for external or internal stimuli to give rise to changes in central signaling pathways. Expression of mesenchymal markers correlates to a bad prognosis and an inferior response to EGFR-TKIs in NSCLC due to the contribution to a resistant phenotype. A deeper understanding of the role of EMT in NSCLC and especially in EGFR-TKI resistance-development constitute one opportunity to improve the benefit of TKI treatment for the individual patient. Many scientific studies have linked the EMT process to EGFR-TKI resistance in NSCLC and our aim is to review the role of EMT in both intrinsic and acquired resistance to EGFR-TKIs.Keywords: Epidermal growth factor receptor (EGFR); epithelial to mesenchymal transition (EMT); non-small cell lung cancer (NSCLC); tyrosine kinase inhibitor (TKI)

show abstract

“…Several growth factors, including Epidermal Growth Factor (EGF) [138][139][140], Insulin-like Growth Factor (IGF) [141][142][143], Platelet-Derived Growth Factor (PDGF) [144,145], and Fibroblast Growth Factor (bFGF) [146,147], can also induce weak, but notable NF-κB activation through their receptors that belong to a family of receptor tyrosine kinases (RTKs). Although the signaling pathways induced by this family of receptors have been intensively studied, the mechanism by which RTKs activate NF-κB is not fully defined, and the functional significance of RTK-induced NF-κB activation in cell proliferation and survival has not been fully appreciated.…”

Section: Cbm Proteins In the Receptor Tyrosine Kinase Pathwaysmentioning

confidence: 99%

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Blonska¹,

Lin²

2010

Cell Res

Self Cite

171

201

View full text Add to dashboard Cite

The NF-κB family of transcription factors plays a crucial role in cell activation, survival and proliferation. Its aberrant activity results in cancer, immunodeficiency or autoimmune disorders. Over the past two decades, tremendous progress has been made in our understanding of the signals that regulate NF-κB activation, especially how scaffold proteins link different receptors to the NF-κB-activating complex, the IκB kinase complex. The growing number of these scaffolds underscores the complexity of the signaling networks in different cell types. In this review, we discuss the role of scaffold molecules in signaling cascades induced by stimulation of antigen receptors, G-protein-coupled receptors and C-type Lectin receptors, resulting in NF-κB activation. Especially, we focus on the family of Caspase recruitment domain (CARD)-containing proteins known as CARMA and their function in activation of NF-κB, as well as the link of these scaffolds to the development of various neoplastic diseases through regulation of NF-κB.

show abstract

Constitutively Active Type I Insulin-Like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and Is Accompanied by an Epithelial-to-Mesenchymal Transition Mediated by NF-κB and Snail

Cited by 217 publications

References 53 publications

Biology of breast cancer during pregnancy using genomic profiling

Biology of breast cancer during pregnancy using genomic profiling

The role of epithelial to mesenchymal transition in resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Contact Info

Product

Resources

About