Epigenetic regulation of RTK signaling

Spangle, Jennifer M.; Roberts, Thomas M.

doi:10.1007/s00109-017-1546-0

Cited by 21 publications

(23 citation statements)

References 51 publications

(54 reference statements)

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“…RTKs are a family of transmembrane proteins with inherent phosphotyrosine kinase activity which remain inactive in the plasma membrane until activated by ligand. The RTK family consists of a number of sub-families, including the epidermal growth factor receptors (EGFRs), platelet derived growth factor receptors (PDGFRs), fibroblast growth factor receptors (FGFRs), vascular endothelial growth factor receptors (VEGFRs), insulin growth factor receptors (IGFRs), and hepatocyte growth factor receptors (HGFRs) [ 84 – 86 ]. Activation of the RTKs by their cognate growth factors, cytokines, hormones or other extracellular signalling molecules, triggers the activation of the PI3K signalling pathway.…”

Section: The Rtk/pi3k/akt Signalling Pathway and Regulation By Ptenmentioning

confidence: 99%

PTEN/PTENP1: ‘Regulating the regulator of RTK-dependent PI3K/Akt signalling’, new targets for cancer therapy

et al. 2018

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Regulation of the PI-3 kinase (PI3K)/Akt signalling pathway is essential for maintaining the integrity of fundamental cellular processes, cell growth, survival, death and metabolism, and dysregulation of this pathway is implicated in the development and progression of cancers. Receptor tyrosine kinases (RTKs) are major upstream regulators of PI3K/Akt signalling. The phosphatase and tensin homologue (PTEN), a well characterised tumour suppressor, is a prime antagonist of PI3K and therefore a negative regulator of this pathway. Loss or inactivation of PTEN, which occurs in many tumour types, leads to overactivation of RTK/PI3K/Akt signalling driving tumourigenesis. Cellular PTEN levels are tightly regulated by a number of transcriptional, post-transcriptional and post-translational regulatory mechanisms. Of particular interest, transcription of the PTEN pseudogene, PTENP1, produces sense and antisense transcripts that exhibit post-transcriptional and transcriptional modulation of PTEN expression respectively. These additional levels of regulatory complexity governing PTEN expression add to the overall intricacies of the regulation of RTK/PI-3 K/Akt signalling. This review will discuss the regulation of oncogenic PI3K signalling by PTEN (the regulator) with a focus on the modulatory effects of the sense and antisense transcripts of PTENP1 on PTEN expression, and will further explore the potential for new therapeutic opportunities in cancer treatment.

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Section: The Rtk/pi3k/akt Signalling Pathway and Regulation By Ptenmentioning

confidence: 99%

PTEN/PTENP1: ‘Regulating the regulator of RTK-dependent PI3K/Akt signalling’, new targets for cancer therapy

et al. 2018

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“…Both genetic and epigenetic modifications in the genes encoding for RTKs are responsible for activation of growth factor-mediated signaling events. This hyperactivation of RTK mediated signaling cascades can even cause cancer [6].…”

Section: Rtk: At the Crossroads Of Cell Growth Proliferation And Differentiationmentioning

confidence: 99%

Recent Advances in the Therapeutic Development of Receptor Tyrosine Kinases (RTK) against Different Types of Cancer

Patranabis¹

2021

Biochemistry

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Receptor Tyrosine Kinases (RTKs) are an important class of receptors involved in regulating different cellular functions. The usual pathway of RTK activation involves specific ligand binding, dimerization and trans-autophosphorylation. Recently, RTK has been extensively studied as they have potential applications in targeted cancer therapy. RTK-based therapeutic strategies are promising because dysfunction of RTK is connected to a variety of diseases. More specifically, RTK has been widely associated with different types of cancer and related diseases. The chapter aims to cover recent advances and challenges in RTK related research, to get an overview of the problems and possibilities associated with targeted therapy. This will help in deciphering novel therapeutic applications in the future.

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“…These alterations result in deregulated kinase activity and malignant transformation [21] and are associated with poor prognosis, drug resistance, cancer metastasis, and lower survival rate. In addition to the contributions of direct genomic events to the expression and hyperactivation of RTKs, epigenetic modifications of RTKs also modulate RTK activity [22,23].…”

Section: Receptor Tyrosine Kinases That Mediate Dsb Repair After Imentioning

confidence: 99%

Targeting DNA Double-Strand Break Repair Pathways to Improve Radiotherapy Response

Toulany

2019

Genes

123

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More than half of cancer patients receive radiotherapy as a part of their cancer treatment. DNA double-strand breaks (DSBs) are considered as the most lethal form of DNA damage and a primary cause of cell death and are induced by ionizing radiation (IR) during radiotherapy. Many malignant cells carry multiple genetic and epigenetic aberrations that may interfere with essential DSB repair pathways. Additionally, exposure to IR induces the activation of a multicomponent signal transduction network known as DNA damage response (DDR). DDR initiates cell cycle checkpoints and induces DSB repair in the nucleus by non-homologous end joining (NHEJ) or homologous recombination (HR). The canonical DSB repair pathways function in both normal and tumor cells. Thus, normal-tissue toxicity may limit the targeting of the components of these two pathways as a therapeutic approach in combination with radiotherapy. The DSB repair pathways are also stimulated through cytoplasmic signaling pathways. These signaling cascades are often upregulated in tumor cells harboring mutations or the overexpression of certain cellular oncogenes, e.g., receptor tyrosine kinases, PIK3CA and RAS. Targeting such cytoplasmic signaling pathways seems to be a more specific approach to blocking DSB repair in tumor cells. In this review, a brief overview of cytoplasmic signaling pathways that have been reported to stimulate DSB repair is provided. The state of the art of targeting these pathways will be discussed. A greater understanding of the underlying signaling pathways involved in DSB repair may provide valuable insights that will help to design new strategies to improve treatment outcomes in combination with radiotherapy.

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Epigenetic regulation of RTK signaling

Cited by 21 publications

References 51 publications

PTEN/PTENP1: ‘Regulating the regulator of RTK-dependent PI3K/Akt signalling’, new targets for cancer therapy

PTEN/PTENP1: ‘Regulating the regulator of RTK-dependent PI3K/Akt signalling’, new targets for cancer therapy

Recent Advances in the Therapeutic Development of Receptor Tyrosine Kinases (RTK) against Different Types of Cancer

Targeting DNA Double-Strand Break Repair Pathways to Improve Radiotherapy Response

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