Growth factors and associated signalling pathways in tumour progression and in cancer treatment

2019 ◽  
pp. 105-122
Author(s):  
Nadège Gaborit ◽  
Yosef Yarden
Keyword(s):  
Growth Factors ◽  
Tyrosine Kinases ◽  
Normal Tissue ◽  
Receptor Tyrosine Kinases ◽  
Tumour Progression ◽  
Signalling Pathways ◽  
Polypeptide Growth Factors ◽  
Growth Factor Signalling ◽  
Approved Drugs ◽  
Nuclear Alterations

To gain increased proliferation, blood supply, invasiveness, and resistance to cytotoxic treatments, cancer cells continuously secrete polypeptide growth factors, or they utilize factors produced by the associated normal tissue and the immunological microenvironment. The growth factors relay biochemical messages by binding with receptor tyrosine kinases (RTKs) located at the cell surface. In response to activation and receptor auto-phosphorylation, RTKs mobilize diverse signalling pathways, which culminate in cytoplasmic and nuclear alterations, including activation of gene expression programmes. This chapter describes several well-characterized growth factors, highlights the cognate receptors and downstream signalling pathways, and exemplifies involvement of specific growth factors in maintenance of the hallmarks of cancer. An account of clinically approved drugs able to intercept growth factor signalling closes this chapter.

Growth factors and associated signalling pathways in tumour progression and in cancer treatment

2019 ◽  
pp. 105-122
Author(s):  
Nadège Gaborit ◽  
Yosef Yarden
Keyword(s):  
Growth Factors ◽  
Tyrosine Kinases ◽  
Normal Tissue ◽  
Receptor Tyrosine Kinases ◽  
Tumour Progression ◽  
Signalling Pathways ◽  
Polypeptide Growth Factors ◽  
Growth Factor Signalling ◽  
Approved Drugs ◽  
Nuclear Alterations

To gain increased proliferation, blood supply, invasiveness, and resistance to cytotoxic treatments, cancer cells continuously secrete polypeptide growth factors, or they utilize factors produced by the associated normal tissue and the immunological microenvironment. The growth factors relay biochemical messages by binding with receptor tyrosine kinases (RTKs) located at the cell surface. In response to activation and receptor auto-phosphorylation, RTKs mobilize diverse signalling pathways, which culminate in cytoplasmic and nuclear alterations, including activation of gene expression programmes. This chapter describes several well-characterized growth factors, highlights the cognate receptors and downstream signalling pathways, and exemplifies involvement of specific growth factors in maintenance of the hallmarks of cancer. An account of clinically approved drugs able to intercept growth factor signalling closes this chapter.

Transmembrane signalling pathways initiating cell growth in fibroblasts

1988 ◽  
Vol 320 (1199) ◽  
pp. 427-436 ◽  
Keyword(s):  
Growth Factor ◽  
Cell Line ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Growth Arrest ◽  
Chinese Hamster ◽  
Signalling Pathways ◽  
Fibroblastic Cell ◽  
Growth Factor Signalling ◽  
Growth Factor Signalling Pathway

The mechanisms of growth factor action were studied in a fibroblastic cell line capable of reversible growth arrest in G0-G1. This cell line, derived from Chinese hamster lung, can be stimulated to divide by a limited set of purified growth factors, including EGF, FGF, PDGF, x-thrombin (THR), serotonin (5-HT) and insulin. THR and 5-HT stimulate, via a G-protein (G p ), a polyphosphoinositide-specific phospholipase C (PtdIns(4,5)P 2 -PLC). In contrast, the mitogens EGF, FGF, PDGF, and insulin do not stimulate PtdIns(4,5)P 2 -PLC, unless this pathway has been preactivated by THR or AIF 4 . Finally, from the specific inhibitory action of pertussis toxin on THR- and 5-HT-induced DNA synthesis, and from the exploitation of the 5-HT pharmacological tools, we conclude that: (i) there are at least two distinct Gproteins involved in signalling growth: G p , coupling receptors to PtdIns(4,5)P 2 -PLC, and G 1 coupling receptors negatively to adenylyl cyclase and probably to other unknown effector(s); (ii) activation of receptor-tyrosine kinases provides an alternate growth factor signalling pathway, independent of G p - and G i -mediated actions; and (iii) tyrosine kinases positively ‘cross-communicate ’ with the inositol-lipid pathway (phosphorylation of G p , PLC, Ptdlns kinases...?).

scholarly journals Receptor Tyrosine Kinases: Role in Cancer Progression

2006 ◽  
Vol 13 (5) ◽  
pp. 191-193
Author(s):  
V. Sangwan ◽  
M. Park
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Progression ◽  
Tyrosine Kinases ◽  
Normal Tissue ◽  
Receptor Tyrosine Kinases ◽  
Tight Control ◽  
Tissue Patterning

Tight control of cell proliferation and morphogenesis in conjunction with programmed cell death (apoptosis) is required to ensure normal tissue patterning. [...]

Cracking the mild, difficult and fiendish codes within and downstream of the EGFR to link diagnostics and therapeutics

2007 ◽  
Vol 35 (1) ◽  
pp. 1-6 ◽  
Author(s):  
M. Waterfield
Keyword(s):  
Signal Transduction ◽  
Growth Factors ◽  
Growth Factor ◽  
Signalling Pathways ◽  
Growth Factor Signalling ◽  
Transduction Mechanisms

Over the last 45 years, I have been working on growth factors, their receptors and signal transduction mechanisms. This period has seen a tremendous growth in knowledge and technology, and all of this, together with a focus interest in oncology, has steered me along a path designed to understand growth factor signalling so that we can see how drugs that target signalling pathways might be able to control cancer. The knowledge that we already have is likely to lead to cures for many common cancers within the next 25 years.

The short and the long: non-coding RNAs and growth factors in cancer progression

2017 ◽  
Vol 45 (1) ◽  
pp. 51-64 ◽  
Author(s):  
Aldema Sas-Chen ◽  
Swati Srivastava ◽  
Yosef Yarden
Keyword(s):  
Growth Factors ◽  
Cancer Progression ◽  
Tumour Progression ◽  
Therapeutic Strategies ◽  
Signalling Pathways ◽  
Circulation System ◽  
Multistep Process ◽  
New Locations ◽  
Non Coding Rnas ◽  
Lines Of Evidence

A relatively well-understood multistep process enables mutation-bearing cells to form primary tumours, which later use the circulation system to colonize new locations and form metastases. However, in which way the emerging abundance of different non-coding RNAs supports tumour progression is poorly understood. Here, we review new lines of evidence linking long and short types of non-coding RNAs to signalling pathways activated in the course of cancer progression by growth factors and by the tumour micro-environment. Resolving the new dimension of non-coding RNAs in oncogenesis will probably translate to earlier detection of cancer and improved therapeutic strategies.

Receptor tyrosine kinases and growth factors expression in tumor thrombus cells in patients with renal cell carcinoma (RCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17073-e17073
Author(s):  
Maria Volkova ◽  
Ilya Tsimafeyeu ◽  
Dmitry Khochenkov ◽  
Anna Olshanskaia ◽  
Niko Vashakmadze ◽  
...  
Keyword(s):  
Growth Factors ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Tyrosine Kinases ◽  
Tumor Thrombus ◽  
Receptor Tyrosine Kinases ◽  
Detection System ◽  
Biological Significance ◽  
Expression Levels ◽  
Lower Expression

e17073 Background: To our knowledge, this is a first study describing the expression of the receptor tyrosine kinases (RTKs) and growth factors (GFs) in venous tumor thrombus cells and comparing results with the expression in primary RCC. Methods: Formalin-fixed paraffin-embedded specimens of tumor thrombus and primary tumor removed from 25 untreated pT3a-T4N0-1M0-1 RCC patients were evaluated by immunohistochemistry with primary antibodies to VEGF-A, FGF2, VEGFR1, VEGFR2, FGFR1, FGFR2, PDGFRα, and PDGFRβ (Abcam/Santa Cruz Biotech) and REAL™ EnVision™ Detection System (Agilent). The extent of expression was compared with 25 specimens of primary tumor tissue (selected from the same patients). Significant differences in the expression among these groups were assessed by chi-squared and Fisher's exact tests using a semi-quantitative method (H-score). The analysis of the correlation between expression levels and RCC characteristics was also performed. Results: Mean age was 62.0 (35-74) years. pT3a, pT3b, pT3c and pT4 stages were detected in 4 (16.0%), 13 (52.0%), 7 (28.0%), and 1 (4.0%) patients. Lymph node metastases were found in 9 (36.0%) cases, 15 (60.0%) patients had 1 or more metastatic sites. All RTKs and GFs were heavily expressed in primary tumor cells. Tumor thrombus cells were characterized by significant lower expression levels of VEGFR1, VEGFR2, and PDGFRα (p < 0.05 for all). Tendency to lower expression of VEGF-A (p = 0.06), FGF-2 (p = 0.046), FGFR1 (p = 0.077), and FGFR2 (p = 0.09) was observed in tumor thrombus cells (Table). VEGFR2 expression levels were 2-times reduced in patients with supradiaphragmatic thrombus (H-score = 21.4±12.0) compared to infradiaphragmatic thrombus (H-score = 55.0±8.5, p = 0.042). Furman grade correlated with the expression levels of VEGFR1 (p = 0.035) and FGFR1 (p = 0.022) in primary tumor cells; tumor invasion into venous wall correlated with the expression levels of VEGFR1 (p = 0.023) and FGFR2 (p = 0.005) in thrombus cells. Conclusions: RCC invasion into veins is accompanied by a decrease in expression of RTKs and GFs. Further studies are needed to understand the biological significance. [Table: see text]

scholarly journals The Role of Insulin-Like Growth Factors and Insulin-Like Growth Factor–Binding Proteins in the Nervous System

2019 ◽  
Vol 12 ◽  
pp. 117862641984217 ◽  
Author(s):  
Moira S Lewitt ◽  
Gary W Boyd
Keyword(s):  
Nervous System ◽  
Growth Factors ◽  
Growth Factor ◽  
Binding Proteins ◽  
Nervous System Development ◽  
Signalling Pathways ◽  
Igf Binding Proteins ◽  
Growth Factor Signalling ◽  
Igf Binding ◽  
Insulin Like Growth Factors

The insulin-like growth factors (IGF-I and IGF-II) and their receptors are widely expressed in nervous tissue from early embryonic life. They also cross the blood brain barriers by active transport, and their regulation as endocrine factors therefore differs from other tissues. In brain, IGFs have paracrine and autocrine actions that are modulated by IGF-binding proteins and interact with other growth factor signalling pathways. The IGF system has roles in nervous system development and maintenance. There is substantial evidence for a specific role for this system in some neurodegenerative diseases, and neuroprotective actions make this system an attractive target for new therapeutic approaches. In developing new therapies, interaction with IGF-binding proteins and other growth factor signalling pathways should be considered. This evidence is reviewed, gaps in knowledge are highlighted, and recommendations are made for future research.

Sign in / Sign up

Export Citation Format

Share Document