Coordination of signalling networks and tumorigenic properties by ABL in glioblastoma cells
The cytoplasmic tyrosine kinase ABL exerts positive or negative effects in solid tumours according to the cellular context, thus functioning as a "switch modulator". The therapeutic effects of drugs targeting a set of signals encompassing ABL have been explored in several solid tumours. However, the...
| Authors: | ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2016 |
| Country: | España |
| Institution: | Universidad de Navarra |
| Repository: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Language: | English |
| OAI Identifier: | oai:dadun.unav.edu:10171/120852 |
| Online Access: | https://hdl.handle.net/10171/120852 |
| Access Level: | Open access |
| Keyword: | ABL RTK signalling Glioblastomas Migration and invasion Tumorigenicity Self-renewal |
| _version_ | 1878740320823279616 |
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| author | Lamballe, F. (Fabienne)|||/items/f8c292e1-952c-4c77-8f46-b294dc088c4d |
| author2 | Toscano, S. (Sara)|||/items/99a06495-7623-499f-9e26-b41f3a8936e1 Conti, F. (Filippo)|||/items/ac5e30b2-3f20-4ddd-b6ec-47b09f810323 Arechederra, M. (María)|||/items/8db5d239-c664-48b0-9bf7-17aa664dd287 Baeza, N. (Nathalie)|||/items/6e097416-05c0-4b77-8249-15e37cd6d0b7 Figarella-Branger, D. (Dominique)|||/items/79428142-41e3-4589-aaa8-63aa4c928458 Helmbacher, F. (Françoise)|||/items/0bbdfa39-a247-4e5d-944d-fd18f8b66fa8 Maina, F. (Flavio)|||/items/6c130d33-d0d3-476b-8b2f-91090237a5d3 |
| author2_role | author author author author author author author |
| author_browse | Arechederra, M. (María)|||/items/8db5d239-c664-48b0-9bf7-17aa664dd287 Baeza, N. (Nathalie)|||/items/6e097416-05c0-4b77-8249-15e37cd6d0b7 Conti, F. (Filippo)|||/items/ac5e30b2-3f20-4ddd-b6ec-47b09f810323 Figarella-Branger, D. (Dominique)|||/items/79428142-41e3-4589-aaa8-63aa4c928458 Helmbacher, F. (Françoise)|||/items/0bbdfa39-a247-4e5d-944d-fd18f8b66fa8 Lamballe, F. (Fabienne)|||/items/f8c292e1-952c-4c77-8f46-b294dc088c4d Maina, F. (Flavio)|||/items/6c130d33-d0d3-476b-8b2f-91090237a5d3 Toscano, S. (Sara)|||/items/99a06495-7623-499f-9e26-b41f3a8936e1 |
| author_facet | Lamballe, F. (Fabienne)|||/items/f8c292e1-952c-4c77-8f46-b294dc088c4d Toscano, S. (Sara)|||/items/99a06495-7623-499f-9e26-b41f3a8936e1 Conti, F. (Filippo)|||/items/ac5e30b2-3f20-4ddd-b6ec-47b09f810323 Arechederra, M. (María)|||/items/8db5d239-c664-48b0-9bf7-17aa664dd287 Baeza, N. (Nathalie)|||/items/6e097416-05c0-4b77-8249-15e37cd6d0b7 Figarella-Branger, D. (Dominique)|||/items/79428142-41e3-4589-aaa8-63aa4c928458 Helmbacher, F. (Françoise)|||/items/0bbdfa39-a247-4e5d-944d-fd18f8b66fa8 Maina, F. (Flavio)|||/items/6c130d33-d0d3-476b-8b2f-91090237a5d3 |
| author_role | author |
| collection | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| description | The cytoplasmic tyrosine kinase ABL exerts positive or negative effects in solid tumours according to the cellular context, thus functioning as a "switch modulator". The therapeutic effects of drugs targeting a set of signals encompassing ABL have been explored in several solid tumours. However, the net contribution of ABL inhibition by these agents remains elusive as these drugs also act on other signalling components. Here, using glioblastoma (GBM) as a cellular paradigm, we report that ABL inhibition exacerbates mesenchymal features as highlighted by down-regulation of epithelial markers and up-regulation of mesenchymal markers. Cells with permanent ABL inhibition exhibit enhanced motility and invasive capabilities, while proliferation and tumorigenic properties are reduced. Intriguingly, permanent ABL inhibition also interferes with GBM neurosphere formation and with expression of stemness markers in sphere-cultured GBM cells. Furthermore, we show that the molecular and biological characteristics of GBM cells with impaired ABL are reversible by restoring ABL levels, thus uncovering a remarkable plasticity of GBM cells to ABL threshold. A phospho-signalling screen revealed that loss of tumorigenic and self-renewal properties in GBM cells under permanent ABL inhibition coincide with drastic changes in the expression and/or phosphorylation levels of multiple signalling components. Our findings identify ABL as a crucial player for migration, invasion, proliferation, tumorigenic, and stem-cell like properties of GBM cells. Taken together, this work supports the notion that the oncogenic role of ABL in GBM cells is associated with its capability to coordinate a signalling setting that determines tumorigenic and stem-cell like properties. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_d0f74ff154fce91d024467aec08c0d01 |
| institution | Universidad de Navarra |
| instname_str | Universidad de Navarra |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:dadun.unav.edu:10171/120852 |
| publishDate | 2016 |
| publishDateSort | 2016 |
| publisher | Rapamycin Press LLC |
| publisherStr | Rapamycin Press LLC |
| reponame_str | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| spelling | Coordination of signalling networks and tumorigenic properties by ABL in glioblastoma cells Lamballe, F. (Fabienne)|||/items/f8c292e1-952c-4c77-8f46-b294dc088c4d Toscano, S. (Sara)|||/items/99a06495-7623-499f-9e26-b41f3a8936e1 Conti, F. (Filippo)|||/items/ac5e30b2-3f20-4ddd-b6ec-47b09f810323 Arechederra, M. (María)|||/items/8db5d239-c664-48b0-9bf7-17aa664dd287 Baeza, N. (Nathalie)|||/items/6e097416-05c0-4b77-8249-15e37cd6d0b7 Figarella-Branger, D. (Dominique)|||/items/79428142-41e3-4589-aaa8-63aa4c928458 Helmbacher, F. (Françoise)|||/items/0bbdfa39-a247-4e5d-944d-fd18f8b66fa8 Maina, F. (Flavio)|||/items/6c130d33-d0d3-476b-8b2f-91090237a5d3 ABL RTK signalling Glioblastomas Migration and invasion Tumorigenicity Self-renewal The cytoplasmic tyrosine kinase ABL exerts positive or negative effects in solid tumours according to the cellular context, thus functioning as a "switch modulator". The therapeutic effects of drugs targeting a set of signals encompassing ABL have been explored in several solid tumours. However, the net contribution of ABL inhibition by these agents remains elusive as these drugs also act on other signalling components. Here, using glioblastoma (GBM) as a cellular paradigm, we report that ABL inhibition exacerbates mesenchymal features as highlighted by down-regulation of epithelial markers and up-regulation of mesenchymal markers. Cells with permanent ABL inhibition exhibit enhanced motility and invasive capabilities, while proliferation and tumorigenic properties are reduced. Intriguingly, permanent ABL inhibition also interferes with GBM neurosphere formation and with expression of stemness markers in sphere-cultured GBM cells. Furthermore, we show that the molecular and biological characteristics of GBM cells with impaired ABL are reversible by restoring ABL levels, thus uncovering a remarkable plasticity of GBM cells to ABL threshold. A phospho-signalling screen revealed that loss of tumorigenic and self-renewal properties in GBM cells under permanent ABL inhibition coincide with drastic changes in the expression and/or phosphorylation levels of multiple signalling components. Our findings identify ABL as a crucial player for migration, invasion, proliferation, tumorigenic, and stem-cell like properties of GBM cells. Taken together, this work supports the notion that the oncogenic role of ABL in GBM cells is associated with its capability to coordinate a signalling setting that determines tumorigenic and stem-cell like properties. Rapamycin Press LLC https://hdl.handle.net/10171/120852 |
| spellingShingle | Coordination of signalling networks and tumorigenic properties by ABL in glioblastoma cells Lamballe, F. (Fabienne)|||/items/f8c292e1-952c-4c77-8f46-b294dc088c4d ABL RTK signalling Glioblastomas Migration and invasion Tumorigenicity Self-renewal |
| title | Coordination of signalling networks and tumorigenic properties by ABL in glioblastoma cells |
| title_full | Coordination of signalling networks and tumorigenic properties by ABL in glioblastoma cells |
| title_fullStr | Coordination of signalling networks and tumorigenic properties by ABL in glioblastoma cells |
| title_full_unstemmed | Coordination of signalling networks and tumorigenic properties by ABL in glioblastoma cells |
| title_short | Coordination of signalling networks and tumorigenic properties by ABL in glioblastoma cells |
| title_sort | Coordination of signalling networks and tumorigenic properties by ABL in glioblastoma cells |
| topic | ABL RTK signalling Glioblastomas Migration and invasion Tumorigenicity Self-renewal |
| topic_facet | ABL RTK signalling Glioblastomas Migration and invasion Tumorigenicity Self-renewal |
| url | https://hdl.handle.net/10171/120852 |