A comprehensive pathway map of epidermal growth factor receptor signaling

Oda, Kanae; Matsuoka, Yoshikazu; Funahashi, Akira; Kitano, Hiroaki

doi:10.1038/msb4100014

Cited by 1,011 publications

(856 citation statements)

References 257 publications

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“…Computational methods for mapping of phosphorylation networks are being developed, and reconstruction of EGFR-mediated pathways have been used to test applicability of such models [32]. Correct network definition may be restricted by the influence of contextual factors, such as subcellular compartmentalization or temporal expression of the proteins involved [33].…”

Section: Discussionmentioning

confidence: 99%

Osteoblast-induced EGFR/ERBB2 signaling in androgen-sensitive prostate carcinoma cells characterized by multiplex kinase activity profiling

Bratland

Boender

Høifødt

et al. 2009

Clin Exp Metastasis

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Bone metastases in prostate cancer are predominantly osteoblastic. To study regulatory mechanisms underlying the establishment of prostate cancer within an osteoblastic microenvironment, human androgen-sensitive prostate carcinoma cells (LNCaP) were treated with culture medium conditioned by human osteoblast-derived sarcoma cells (OHS), and activated signalling pathways in the carcinoma cells were analyzed using microarrays with tyrosine kinase substrates. Network interaction analysis of substrates with significantly increased phosphorylation levels revealed that signalling pathways mediated by EGFR and ERBB2 were activated in LNCaP cells under OHS influence but also by androgen treatment. Activation of EGFR/ERBB2 signalling was also found in LNCaP cells in cocultures with OHS cells or osteoblastic cells that had been differentiated from human mesenchymal stem cells. Our experimental data suggests osteoblast-directed induction of signalling activity via EGFR and ERBB2 in prostate carcinoma cells and may provide a rationale for the use of EGFR or ERBB2 inhibition in systemic prevention or treatment of metastatic prostate cancer in the androgensensitive stage of the disease.

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Section: Discussionmentioning

confidence: 99%

Osteoblast-induced EGFR/ERBB2 signaling in androgen-sensitive prostate carcinoma cells characterized by multiplex kinase activity profiling

Bratland

Boender

Høifødt

et al. 2009

Clin Exp Metastasis

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“…multiple upstream signal transduction pathways converge and then spread out again to form downstream pathways, which then affect multiple cellular events. These bow-tie structures are also observed in maps showing the signal transduction pathways after Toll like receptor (TLR) and EGFR stimulation [14,35]. This suggests that, in some instances, the most important process within a system may be identified by examining the structure of comprehensive pathway maps.…”

Section: Currently Reported Comprehensive Pathway Mapsmentioning

confidence: 85%

“…In addition, numerous somatic mutations have been reported in genes, which are associated with the development of cancer [12]. However, irrespective of such efforts, we still do not fully understand the mechanisms for the development of diseases, since multiple factors are often responsible for the disease development [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Systems‐based understanding of pharmacological responses with combinations of multidisciplinary methodologies

Kariya

Honma

Suzuki

2013

Biopharm & Drug Disp

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The importance of systems-based pharmacological approaches to drug discovery and development has increasingly been recognized. This reviews summarizes recent advances in the development of systems pharmacology and introduces the methods used for analysis. To understand the cellular response at the molecular level, pathway maps must be prepared to show how the function of the constituent molecules within cells are linked and integrated to form molecular networks. First, the methods used to prepare these pathway maps, such as databases, knowledge bases and software platforms, are introduced. Then the mathematical theories used to analyse the behavior of molecular networks are summarized. To quantitatively predict cellular responses, simulations are performed that are based on the rate equations for each reaction within the pathway map. If the number of reactions described in the pathway map is small, and if the parameter values for the rate constants are available, it is possible accurately to simulate the behavior of the molecular networks. However, to analyse complex maps, mathematical abstraction is required. Such abstraction methods are important to integrate cellular responses and to understand tissue/organ and in vivo pharmacological/toxicological responses. The scope and limitations of the methods are also discussed.

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“…The size of microfluidic systems increases the speed of common experimental techniques, such as protein and DNA electrophoresis, by orders of magnitude. 9 Additionally, the 3 The entire map of the EGFR pathway is quite large but demonstrates how intracellular components interact to trigger events.…”

Section: Introductionmentioning

confidence: 99%

Microfluidics-based systems biology

2006

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Systems biology seeks to develop a complete understanding of cellular mechanisms by studying the functions of intra-and inter-cellular molecular interactions that trigger and coordinate cellular events. However, the complexity of biological systems causes accurate and precise systems biology experimentation to be a difficult task. Most biological experimentation focuses on highly detailed investigation of a single signaling mechanism, which lacks the throughput necessary to reconstruct the entirety of the biological system, while high-throughput testing often lacks the fidelity and detail necessary to fully comprehend the mechanisms of signal propagation. Systems biology experimentation, however, can benefit greatly from the progress in the development of microfluidic devices. Microfluidics provides the opportunity to study cells effectively on both a single-and multi-cellular level with high-resolution and localized application of experimental conditions with biomimetic physiological conditions. Additionally, the ability to massively array devices on a chip opens the door for high-throughput, high fidelity experimentation to aid in accurate and precise unraveling of the intertwined signaling systems that compose the inner workings of the cell.

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A comprehensive pathway map of epidermal growth factor receptor signaling

Cited by 1,011 publications

References 257 publications

Osteoblast-induced EGFR/ERBB2 signaling in androgen-sensitive prostate carcinoma cells characterized by multiplex kinase activity profiling

Osteoblast-induced EGFR/ERBB2 signaling in androgen-sensitive prostate carcinoma cells characterized by multiplex kinase activity profiling

Systems‐based understanding of pharmacological responses with combinations of multidisciplinary methodologies

Microfluidics-based systems biology

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