Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling
Increasing evidence indicates that success of targeted therapies in the treatment of cancer is context-dependent and is influenced by a complex crosstalk between signaling pathways and between cell types in the tumor. The Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) signaling axis highlights t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/5/1201 |
| _version_ | 1827692590204452864 |
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| author | Harriet R. Ferguson Michael P. Smith Chiara Francavilla |
| author_facet | Harriet R. Ferguson Michael P. Smith Chiara Francavilla |
| author_sort | Harriet R. Ferguson |
| collection | DOAJ |
| description | Increasing evidence indicates that success of targeted therapies in the treatment of cancer is context-dependent and is influenced by a complex crosstalk between signaling pathways and between cell types in the tumor. The Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) signaling axis highlights the importance of such context-dependent signaling in cancer. Aberrant FGFR signaling has been characterized in almost all cancer types, most commonly non-small cell lung cancer (NSCLC), breast cancer, glioblastoma, prostate cancer and gastrointestinal cancer. This occurs primarily through amplification and over-expression of <i>FGFR1</i> and <i>FGFR2</i> resulting in ligand-independent activation. Mutations and translocations of <i>FGFR1-4</i> are also identified in cancer. Canonical FGF-FGFR signaling is tightly regulated by ligand-receptor combinations as well as direct interactions with the FGFR coreceptors heparan sulfate proteoglycans (HSPGs) and Klotho. Noncanonical FGFR signaling partners have been implicated in differential regulation of FGFR signaling. FGFR directly interacts with cell adhesion molecules (CAMs) and extracellular matrix (ECM) proteins, contributing to invasive and migratory properties of cancer cells, whereas interactions with other receptor tyrosine kinases (RTKs) regulate angiogenic, resistance to therapy, and metastatic potential of cancer cells. The diversity in FGFR signaling partners supports a role for FGFR signaling in cancer, independent of genetic aberration. |
| first_indexed | 2024-03-10T11:25:14Z |
| format | Article |
| id | doaj.art-d2cda442a4804ac0a8849a696332b2d3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T11:25:14Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d2cda442a4804ac0a8849a696332b2d32023-11-21T19:42:48ZengMDPI AGCells2073-44092021-05-01105120110.3390/cells10051201Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer SignalingHarriet R. Ferguson0Michael P. Smith1Chiara Francavilla2Division of Molecular and Cellular Function, School of Biological Science, Faculty of Biology Medicine and Health (FBMH), The University of Manchester, Manchester M13 9PT, UKDivision of Molecular and Cellular Function, School of Biological Science, Faculty of Biology Medicine and Health (FBMH), The University of Manchester, Manchester M13 9PT, UKDivision of Molecular and Cellular Function, School of Biological Science, Faculty of Biology Medicine and Health (FBMH), The University of Manchester, Manchester M13 9PT, UKIncreasing evidence indicates that success of targeted therapies in the treatment of cancer is context-dependent and is influenced by a complex crosstalk between signaling pathways and between cell types in the tumor. The Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) signaling axis highlights the importance of such context-dependent signaling in cancer. Aberrant FGFR signaling has been characterized in almost all cancer types, most commonly non-small cell lung cancer (NSCLC), breast cancer, glioblastoma, prostate cancer and gastrointestinal cancer. This occurs primarily through amplification and over-expression of <i>FGFR1</i> and <i>FGFR2</i> resulting in ligand-independent activation. Mutations and translocations of <i>FGFR1-4</i> are also identified in cancer. Canonical FGF-FGFR signaling is tightly regulated by ligand-receptor combinations as well as direct interactions with the FGFR coreceptors heparan sulfate proteoglycans (HSPGs) and Klotho. Noncanonical FGFR signaling partners have been implicated in differential regulation of FGFR signaling. FGFR directly interacts with cell adhesion molecules (CAMs) and extracellular matrix (ECM) proteins, contributing to invasive and migratory properties of cancer cells, whereas interactions with other receptor tyrosine kinases (RTKs) regulate angiogenic, resistance to therapy, and metastatic potential of cancer cells. The diversity in FGFR signaling partners supports a role for FGFR signaling in cancer, independent of genetic aberration.https://www.mdpi.com/2073-4409/10/5/1201FGFRsFGFssignalingcancertumorigenesiscoreceptors |
| spellingShingle | Harriet R. Ferguson Michael P. Smith Chiara Francavilla Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling Cells FGFRs FGFs signaling cancer tumorigenesis coreceptors |
| title | Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling |
| title_full | Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling |
| title_fullStr | Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling |
| title_full_unstemmed | Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling |
| title_short | Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling |
| title_sort | fibroblast growth factor receptors fgfrs and noncanonical partners in cancer signaling |
| topic | FGFRs FGFs signaling cancer tumorigenesis coreceptors |
| url | https://www.mdpi.com/2073-4409/10/5/1201 |
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