Fibroblast growth factors, their receptors and signaling.

doi:10.1677/ERC.0.0070165

Home
/
Papers
/
Fibroblast growth factors, their receptors and signaling.

Journal Article•DOI•

Fibroblast growth factors, their receptors and signaling.

Ciaran Powers¹, S W McLeskey, Anton Wellstein¹•Institutions (1)

Georgetown University¹

01 Sep 2000-Endocrine-related Cancer (Bioscientifica Ltd)-Vol. 7, Iss: 3, pp 165-197

TL;DR: FGF signaling also appears to play a role in tumor growth and angiogenesis, and autocrine FGF signaling may be particularly important in the progression of steroid hormone-dependent cancers to a hormone-independent state.

read less

Abstract: Fibroblast growth factors (FGFs) are small polypeptide growth factors, all of whom share in common certain structural characteristics, and most of whom bind heparin avidly. Many FGFs contain signal peptides for secretion and are secreted into the extracellular environment, where theycan bind to the heparan-like glycosaminoglycans (HLGAGs) of the extracellular matrix (ECM). From this reservoir, FGFs mayact directlyon target cells, or theycan be released through digestion of the ECM or the activityof a carrier protein, a secreted FGF binding protein. FGFs bind specific receptor tyrosine kinases in the context of HLGAGs and this binding induces receptor dimerization and activation, ultimatelyresulting in the activation of various signal transduction cascades. Some FGFs are potent angiogenic factors and most playimportant roles in embry onic development and wound healing. FGF signaling also appears to playa role in tumor growth and angiogenesis, and autocrine FGF signaling maybe particularlyimportant in the progression of steroid hormone-dependent cancers to a hormone-independent state.

...read moreread less

Content maybe subject to copyright Report

Citations

PDF

Open Access

More filters

Journal Article•DOI•

Immunolocalization of FGF-2, -7, -8, -10 and FGFR-1–4 during regeneration of the rat submandibular gland

[...]

Osamu Shimizu¹, Tomohiro Yasumitsu¹, Hiroshi Shiratsuchi¹, Shunichi Oka¹, Tatsuhisa Watanabe¹, Tadahito Saito¹, Yoshiyuki Yonehara¹ - Show less +3 more•Institutions (1)

Nihon University¹

15 Jul 2015-Journal of Molecular Histology

TL;DR: It is suggested that FGF-2, -7, -8 and -10 play important roles in NFAC, MAC, and DLS through FGFR-1 and -4 during regeneration of submandibular gland.

...read moreread less

Abstract: Fibroblast growth factors (FGFs) and their receptors (FGFRs) play important roles in the development of the submandibular gland. Although regeneration of submandibular glands follows a similar process to their development, it is unknown how FGFs and FGFRs are distributed during regeneration of submandibular gland. The aim of this study was to determine the localization of FGFs and FGFRs during such regenerative processes. After 7 days’ obstruction, the submandibular glands were collected at days 0, 1, 3, 7, 11 and 14 after duct release to study regeneration. The regenerative processes of the submandibular gland were investigated by immunohistochemistry for FGF-2, 7, 8, 10 and FGFR-1–4. Immunohistochemical staining revealed that FGF-2 was moderately expressed in the epithelial cells of duct-like structures (DLS) and newly formed acinar cells (NFAC) at days 0–7, and strongly in intercalated duct (ICD) at control gland and Day 7–14. FGF-7 was localized moderately in NFAC and DLS. FGF-8 was localized moderately in the epithelial cells of DLS during regeneration. Strong positive immunoreactions for FGF-10 were found in NFAC and the epithelial cells of DLS during regeneration, as well as the ICD and lateral surfaces of the maturing acinar cells (MAC). FGFR-1 was expressed moderately in the ICD, and weakly in the NFAC and MAC. Positive immunoreactions for FGFR-2 were not observed during regeneration. Additionally, FGFR-4 was detected strongly in the ICD and slightly in NFAC. These findings suggest that FGF-2, -7, -8 and -10 play important roles in NFAC, MAC, and DLS through FGFR-1 and -4 during regeneration of submandibular gland.

...read moreread less

8 citations

Cites background from "Fibroblast growth factors, their re..."

...Because FGFR-3 does not bind FGF-10 (Powers et al. 2000) and no submandibular gland phenotype has been reported in the FGFR-3 null mouse (Colvin et al. 1996; Deng et al. 1996), it is unclear whether FGFR-3 has a role in regeneration, which will be investigated in the future studies....
[...]
...It has been reported that FGF-10 binds with high affinity to FGFR-1 (Igarashi et al. 1998; Powers et al. 2000) and FGFR-2 (Yeh et al. 2003)....
[...]
...It has been reported that FGF-10 binds with high affinity to FGFR-1 (Igarashi et al. 1998; Powers et al. 2000) and FGFR-2 (Yeh et al....
[...]
...Because FGFR-3 does not bind FGF-10 (Powers et al. 2000) and no submandibular gland phenotype has been reported in the FGFR-3 null mouse (Colvin et al....
[...]

Dissertation•

Molecular cloning and functional studies of tenascin-C isoforms containing the fibronectin-type III repeat additional domain 1 (AD1)

[...]

David Stephen Guttery

03 Jul 2009

TL;DR: High MW TNC isoforms including AD1 have been associated with more aggressive features of breast carcinomas and in-vitro with an invasive phenotype and PFN1 is identified as a novel gene target associated with tumours that express high levels of TNC-14/16.

...read moreread less

Abstract: Tenascin-C is an extracellular matrix glycoprotein expressed at low levels in normal breast tissue and highly expressed in both the stroma and malignant cells of solid tumours. Multiple isoforms of TNC are generated by alternative splicing. The aim of this study was: 1) to investigate the expression of key high molecular weight (MW) TNC isoforms containing domains D, B/D, AD1 and AD2 in normal, benign and malignant breast and relate expression to histopathological features, 2) to investigate the functional significance of AD1 by molecular cloning and 2D invasion assays, 3) to perform differential gene expression analysis using GeneChip arrays and relate to expression of high MW TNC isoforms in MCF-7 cells. AD1 and AD2 were detected in all TNC positive breast cell lines, normal and tumour breast tissues and isolated cells from normal breast tissue, with myoepithelial cells being the major source of AD1. In carcinomas, expression of high MW TNC was significantly associated with younger age (≤ 40 years; p = < 0.05 for all isoforms), negative ER (p = 0.011 for AD1 and 0.032 for AD1/AD2 respectively) and high grade (p = 0.017 and 0.019 respectively). Expression of total TNC, TNC-9/16 and TNC14/16 was also associated with negative CK14 (p = 0.003 for all), and higher TNC14/16 expression was associated with lobular carcinomas (p = 0.004). Molecular cloning of AD1 and transfection studies using the TNC-14/AD1/16 isoform significantly increased MCF-7 cell invasion to a level comparable to TNC-9/14/16 (p = < 0.001). Differential gene expression analysis showed that TNC-9/14/16 and TNC14/AD1/16 significantly increased expression of interferon-inducible transmembrane protein 1 (IFITM1) and profilin-1 (PFN1) in transfected MCF-7 cells. However, quantitative RT-PCR analysis of tissue samples showed significant down-regulation of PFN1 in tumours, compared to normal breast (p = 0.02), which was significantly associated with high TNC-14/16 expression (p = 0.002). In conclusion, high MW TNC isoforms including AD1 have been associated with more aggressive features of breast carcinomas and in-vitro with an invasive phenotype. Moreover, this study also identifies PFN1 as a novel gene target associated with tumours that express high levels of TNC-14/16.

...read moreread less

8 citations

Cites background from "Fibroblast growth factors, their re..."

...The FGF signalling axis comprises 18 functionally defined ligands and four FGFRs, many of which have multiple isoforms that are made up mostly of alternative splicing in the third extracellular immunoglobulin-like domains (Powers et al., 2000; Ornitz and Itoh, 2001)....
[...]

Dissertation•

The role of Beta-adrenoceptor (βAR) antagonists in promoting healing of chronic wounds

[...]

Waseem Ali Hasan Al-Jumaili

27 Jun 2018

8 citations

Cites background from "Fibroblast growth factors, their re..."

...FGF2 has an important role in wound healing by regulating tissue remodelling and formation (Powers et al., 2000)....
[...]
...In wound healing, FGF2 plays an important role in granulation tissue formation and reepithelialization (Powers et al., 2000)....
[...]

Journal Article•DOI•

Crumbs3 is a critical factor that regulates invasion and metastasis of colon adenocarcinoma via the specific interaction with FGFR1.

[...]

Hidekazu Iioka¹, Ken Saito¹, Masakiyo Sakaguchi², Taro Tachibana³, Keiichi Homma, Eisaku Kondo¹ - Show less +2 more•Institutions (3)

Niigata University¹, Okayama University², Osaka City University³

15 Nov 2019-International Journal of Cancer

TL;DR: It is demonstrated that Crb3 strongly promotes tumor invasion and metastasis of human colon adenocarcinoma cells through specific interaction to FGFR1 on colon cancer cells.

...read moreread less

Abstract: Epithelial cell polarity regulator Crumbs3 (Crb3), a mammalian homolog within the Drosophila Crb gene family, was initially identified as an essential embryonic development factor. It is recently implicated in tumor suppression, though its specific functions are controversial. We here demonstrate that Crb3 strongly promotes tumor invasion and metastasis of human colon adenocarcinoma cells. Crb3 centrality to tumor migration was supported by strong expression at invasive front and metastatic foci of colonic adenocarcinoma of the patient tissues. Accordingly, two different Crb3-knockout (KO) lines, Crb3-KO (Crb3 -/-) DLD-1 and Crb3-KO WiDr from human colonic adenocarcinomas, were generated by the CRISPR-Cas9 system. Crb3-KO DLD-1 cells exhibited loss of cellular mobility in vitro and dramatic suppression of liver metastases in vivo in contrast to the wild type of DLD-1. Unlike DLD-1, Crb3-KO WiDr mobility and metastasis were unaffected, which were similar to wild-type WiDr. Proteome analysis of Crb3-coimmunopreciptated proteins identified different respective fibroblast growth factor receptor (FGFR) isotypes specifically bound to Crb3 isoform a through their intracellular domain. In DLD-1, Crb3 showed membranous localization of FGFR1 leading to its functional activation, whereas Crb3 bound to cytoplasmic FGFR4 in WiDr without FGFR1 expression, leading to cellular growth. Correlative expression between Crb3 and FGFR1 was consistently detected in primary and metastatic colorectal cancer patient tissues. Taking these together, Crb3 critically accelerates cell migration, namely invasion and metastasis of human colon cancers, through specific interaction to FGFR1 on colon cancer cells.

...read moreread less

8 citations

Cites background from "Fibroblast growth factors, their re..."

...The family consists of four genes and its tyrosine kinase activity is regulated in a context-dependent manner.(14,15) Tumor patient tissue etiology also revealed that FGFR signaling component activation was the most commonly observed....
[...]

Journal Article•DOI•

The role of SYT-SSX fusion gene in tumorigenesis of synovial sarcoma.

[...]

Xiao Feng¹, Yalan Huang¹, Zhen Zhang¹, Ning Wang¹, Qing Yao¹, Lijuan Pang¹, Feng Li², Feng Li¹, Yan Qi¹ - Show less +5 more•Institutions (2)

Shihezi University¹, Capital Medical University²

01 Jun 2021-Pathology Research and Practice

TL;DR: In this paper, the relationship between the SYT-SSX fusion gene and the related pathway molecules as well as other molecules involved from different perspectives, which may provide a deeper and clearer understanding of the syt-SS X fusion gene function.

...read moreread less

Abstract: Synovial sarcoma (SS) is an aggressive malignancy of an unknown tissue origin that is characterized by biphasic differentiation. A possible basis of the pathogenesis of SS is pathognomonic t(X;18) (p11.2; q11.2) translocation, leading to the formation and expression of the SYT-SSX fusion gene. More than a quarter of the patients die of SS metastasis within 5 years after the diagnosis, but the pathogenic factors are unknown. Therefore, there is an urgent need to explore the pathogenesis, invasion, metastasis, and clinical treatment options for SS, especially molecular-targeted drug therapy. Recent studies have shown that the SYT-SSX fusion gene associated with SS may be regulated by different signaling pathways, microRNAs, and other molecules, which may produce stem cell characteristics or promote epithelial-mesenchymal transition, resulting in SS invasion and metastasis. This review article aims to show the relationship between the SYT-SSX fusion gene and the related pathway molecules as well as other molecules involved from different perspectives, which may provide a deeper and clearer understanding of the SYT-SSX fusion gene function. Therefore, this review may provide a more innovative and broader perspective of the current research, treatment options, and prognosis assessment of SS.

...read moreread less

8 citations

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
…
179
180
181
182
183
184
185
…
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200

Collapse

References

PDF

Open Access

More filters

Journal Article•DOI•

Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.

[...]

Avner Yayon¹, Michael Klagsbrun², Jeffrey D. Esko³, Philip Leder⁴, David M. Ornitz⁴ - Show less +1 more•Institutions (4)

Weizmann Institute of Science¹, Harvard University², University of Alabama at Birmingham³, Howard Hughes Medical Institute⁴

22 Feb 1991-Cell

TL;DR: It is demonstrated that free heparin and heparan sulfate can reconstitute a low affinity receptor that is, in turn, required for the high affinity binding of bFGF.

...read moreread less

2,448 citations

Journal Article•DOI•

Protein modules and signalling networks

[...]

Tony Pawson¹•Institutions (1)

Mount Sinai Hospital, Toronto¹

16 Feb 1995-Nature

TL;DR: This work highlights conserved protein domains that act as key regulatory participants in many of these different signalling pathways in multicellular organisms.

...read moreread less

Abstract: Communication between cells assumes particular importance in multicellular organisms. The growth, migration and differentiation of cells in the embryo, and their organization into specific tissues, depend on signals transmitted from one cell to another. In the adult, cell signalling orchestrates normal cellular behaviour and responses to wounding and infection. The consequences of breakdowns in this signalling underlie cancer, diabetes and disorders of the immune and cardiovascular systems. Conserved protein domains that act as key regulatory participants in many of these different signalling pathways are highlighted.

...read moreread less

2,433 citations

"Fibroblast growth factors, their re..." refers background in this paper

...One way these recruited target proteins may be localized to the activated receptor is through the interaction between their Src-homology 2 (SH2) domains and specific phosphotyrosine residues on the activated receptor (Pawson 1995)....
[...]
...Phosphorylated tyrosine residues, in turn, recruit other signaling molecules to the activated receptors and propagate the signal through many possible transduction pathways (Pawson 1995)....
[...]

Journal Article•DOI•

Thalidomide is an inhibitor of angiogenesis.

[...]

Robert J. D'Amato¹, Michael S. Loughnan, Evelyn Flynn, Judah Folkman•Institutions (1)

Harvard University¹

26 Apr 1994-Proceedings of the National Academy of Sciences of the United States of America

TL;DR: Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of Thalidomid-treated embryos.

...read moreread less

Abstract: Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide is an inhibitor of angiogenesis induced by basic fibroblast growth factor in a rabbit cornea micropocket assay. Experiments including the analysis of thalidomide analogs revealed that the antiangiogenic activity correlated with the teratogenicity but not with the sedative or the mild immunosuppressive properties of thalidomide. Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of thalidomide-treated embryos. These experiments shed light on the mechanism of thalidomide's teratogenicity and hold promise for the potential use of thalidomide as an orally administered drug for the treatment of many diverse diseases dependent on angiogenesis.

...read moreread less

2,364 citations

Journal Article•DOI•

Receptor specificity of the fibroblast growth factor family.

[...]

David M. Ornitz¹, Jingsong Xu¹, Jennifer S. Colvin¹, Donald G. McEwen¹, Craig A. MacArthur¹, François Coulier², Guangxia Gao³, Mitchell Goldfarb⁴ - Show less +4 more•Institutions (4)

Washington University in St. Louis¹, French Institute of Health and Medical Research², Columbia University³, Icahn School of Medicine at Mount Sinai⁴

21 Jun 1996-Journal of Biological Chemistry

TL;DR: It is demonstrated that FGF 1 is the only FGF that can activate all FGF receptor splice variants and the relative activity of all the other members of the FGF family is determined.

...read moreread less

2,066 citations

"Fibroblast growth factors, their re..." refers background in this paper

...†From Ornitz et al. (1996), except where stated; ‡From Koga et al. (1995); §From Miralles et al. (1999); ¶From Xu et al. (1999). topologically identical to interleukin-1β (IL-1β) (Zhu et al. 1991), with which some members also share the feature of secretion by an endoplasmic reticulum…...
[...]
...Mutation of all four cysteines to serines results in a protein with the same secondary structure and equally mitogenic for 3T3 cells as the wild-type FGF-2 (Foxet al. 1988), suggesting that the formation of disulfide bridges is not important for the secondary structure and mitogenic activity of…...
[...]
...Ornitz et al. (1996) determined the specificity of different FGFs for different receptor isoforms by overexpressing these isoforms in Baf3 cells, which do not normally express FGFRs, and assaying for [3H]thymidine incorporation in these cells following treatment with different FGFs (see Table 2)....
[...]
...1, IIIb 100 60 34 16 4 5 6 4 4 1, IIIc 100 104 0 102 59 55 0 1 21 2, IIIb 100 9 45 15 5 5 81 4 7 2, IIIc 100 64 4 94 25 61 2.5 16 89 3, IIIb 100 1 2 1 1 1 1 1 42 3, IIIc 100 107 1 69 12 9 1 41 96 4 100 113 6 108 7 79 2 76 75 Modified from Ornitz et al. (1996)....
[...]

Journal Article•DOI•

The heparin-binding (fibroblast) growth factor family of proteins.

[...]

Wilson H. Burgess, Thomas Maciag

01 Jan 1989-Annual Review of Biochemistry

1,994 citations

"Fibroblast growth factors, their re..." refers background in this paper

...Defining features of the FGF family are a strong affinity for heparin and HLGAGs (Burgess & Maciag 1989), as well as a central core of 140 amino acids that is highly homologous between different family members....
[...]