Fragile X mental retardation protein in intrahepatic cholangiocarcinoma: regulating the cancer cell behavior plasticity at the leading edge
Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy of the intrahepatic biliary tract with a very poor prognosis. Although some clinicopathological parameters can be prognostic factors for iCCA, the molecular prognostic markers and potential mechanisms of iCCA have not been well investigated...
| Autores: | , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/114702 |
| Acceso en línea: | https://hdl.handle.net/10171/114702 |
| Access Level: | acceso abierto |
| Palabra clave: | Intrahepatic cholangiocarcinoma (iCCA) Fragile X mental retardation protein (FMRP) Cancers |
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Fragile X mental retardation protein in intrahepatic cholangiocarcinoma: regulating the cancer cell behavior plasticity at the leading edgeCarotti, S. (Simone)|||/items/f8485483-e922-4fca-b9c7-39dbe5bf6342Zingariello, M. (Maria)|||/items/b623e94b-bc53-4012-8f59-c257d6b8af7bFrancesconi, M. (Maria)|||/items/102d1263-2a4e-4bb3-a781-37f0df819b64D’Andrea, L. (Laura)|||/items/fdc5db8f-0222-477a-bdee-c92d2fadd88aLatasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356Colyn, L. (Leticia)|||/items/5972aa59-9877-442f-b405-1d4af39847dbFernández-Barrena, M.G. (Maite G.)|||/items/cfa77580-40b9-43a4-b237-b234ef7fb6cbFlammia, R.S. (Rocco Simone)|||/items/88a236d9-bd71-4050-a1b9-1645ca9ef09fFalchi, M. (Mario)|||/items/0e9e3a04-f8ea-43b6-af48-da4ddbe0aae0Righi, D. (Daniela)|||/items/d332963f-65c8-4e85-8c8e-12ba45f625d0Pedini, G. (Giorgia)|||/items/eeeeb8a5-e51f-4bcb-af23-b39951ef1054Pantano, F. (Francesco)|||/items/8b8cffeb-f8a5-410f-b43d-ed67d4677a23Bagni, C. (Claudia)|||/items/108ec5ce-f725-400f-a02f-2ae800d2dc79Perrone, G. (Giuseppe)|||/items/902a6a22-bf18-40f4-a470-6ae8bc4a9ed9Rana, R.A. (Rosa Alba)|||/items/a8822cf9-e765-4a21-924e-a6e2ef105b7dAvila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419fMorini, S. (Sergio)|||/items/e5ce1f9e-6846-45ea-8583-6555829fbf10Zalfa, F. (Francesca)|||/items/14da61f4-6c4a-41f6-ab47-c162a3474d60Intrahepatic cholangiocarcinoma (iCCA)Fragile X mental retardation protein (FMRP)CancersIntrahepatic cholangiocarcinoma (iCCA) is a rare malignancy of the intrahepatic biliary tract with a very poor prognosis. Although some clinicopathological parameters can be prognostic factors for iCCA, the molecular prognostic markers and potential mechanisms of iCCA have not been well investigated. Here, we report that the Fragile X mental retardation protein (FMRP), a RNA binding protein functionally absent in patients with the Fragile X syndrome (FXS) and also involved in several types of cancers, is overexpressed in human iCCA and its expression is significantly increased in iCCA metastatic tissues. The silencing of FMRP in metastatic iCCA cell lines affects cell migration and invasion, suggesting a role of FMRP in iCCA progression. Moreover, we show evidence that FMRP is localized at the invasive front of human iCCA neoplastic nests and in pseudopodia and invadopodia protrusions of migrating and invading iCCA cancer cells. Here FMRP binds several mRNAs encoding key proteins involved in the formation and/or function of these protrusions. In particular, we find that FMRP binds to and regulates the expression of Cortactin, a critical regulator of invadopodia formation. Altogether, our findings suggest that FMRP could promote cell invasiveness modulating membrane plasticity and invadopodia formation at the leading edges of invading iCCA cells.MacMillan PressDadun. Depósito Académico Digital Universidad de Navarra20212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/114702reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/1147022026-06-21T12:47:57Z |
| dc.title.none.fl_str_mv |
Fragile X mental retardation protein in intrahepatic cholangiocarcinoma: regulating the cancer cell behavior plasticity at the leading edge |
| title |
Fragile X mental retardation protein in intrahepatic cholangiocarcinoma: regulating the cancer cell behavior plasticity at the leading edge |
| spellingShingle |
Fragile X mental retardation protein in intrahepatic cholangiocarcinoma: regulating the cancer cell behavior plasticity at the leading edge Carotti, S. (Simone)|||/items/f8485483-e922-4fca-b9c7-39dbe5bf6342 Intrahepatic cholangiocarcinoma (iCCA) Fragile X mental retardation protein (FMRP) Cancers |
| title_short |
Fragile X mental retardation protein in intrahepatic cholangiocarcinoma: regulating the cancer cell behavior plasticity at the leading edge |
| title_full |
Fragile X mental retardation protein in intrahepatic cholangiocarcinoma: regulating the cancer cell behavior plasticity at the leading edge |
| title_fullStr |
Fragile X mental retardation protein in intrahepatic cholangiocarcinoma: regulating the cancer cell behavior plasticity at the leading edge |
| title_full_unstemmed |
Fragile X mental retardation protein in intrahepatic cholangiocarcinoma: regulating the cancer cell behavior plasticity at the leading edge |
| title_sort |
Fragile X mental retardation protein in intrahepatic cholangiocarcinoma: regulating the cancer cell behavior plasticity at the leading edge |
| dc.creator.none.fl_str_mv |
Carotti, S. (Simone)|||/items/f8485483-e922-4fca-b9c7-39dbe5bf6342 Zingariello, M. (Maria)|||/items/b623e94b-bc53-4012-8f59-c257d6b8af7b Francesconi, M. (Maria)|||/items/102d1263-2a4e-4bb3-a781-37f0df819b64 D’Andrea, L. (Laura)|||/items/fdc5db8f-0222-477a-bdee-c92d2fadd88a Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Colyn, L. (Leticia)|||/items/5972aa59-9877-442f-b405-1d4af39847db Fernández-Barrena, M.G. (Maite G.)|||/items/cfa77580-40b9-43a4-b237-b234ef7fb6cb Flammia, R.S. (Rocco Simone)|||/items/88a236d9-bd71-4050-a1b9-1645ca9ef09f Falchi, M. (Mario)|||/items/0e9e3a04-f8ea-43b6-af48-da4ddbe0aae0 Righi, D. (Daniela)|||/items/d332963f-65c8-4e85-8c8e-12ba45f625d0 Pedini, G. (Giorgia)|||/items/eeeeb8a5-e51f-4bcb-af23-b39951ef1054 Pantano, F. (Francesco)|||/items/8b8cffeb-f8a5-410f-b43d-ed67d4677a23 Bagni, C. (Claudia)|||/items/108ec5ce-f725-400f-a02f-2ae800d2dc79 Perrone, G. (Giuseppe)|||/items/902a6a22-bf18-40f4-a470-6ae8bc4a9ed9 Rana, R.A. (Rosa Alba)|||/items/a8822cf9-e765-4a21-924e-a6e2ef105b7d Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f Morini, S. (Sergio)|||/items/e5ce1f9e-6846-45ea-8583-6555829fbf10 Zalfa, F. (Francesca)|||/items/14da61f4-6c4a-41f6-ab47-c162a3474d60 |
| author |
Carotti, S. (Simone)|||/items/f8485483-e922-4fca-b9c7-39dbe5bf6342 |
| author_facet |
Carotti, S. (Simone)|||/items/f8485483-e922-4fca-b9c7-39dbe5bf6342 Zingariello, M. (Maria)|||/items/b623e94b-bc53-4012-8f59-c257d6b8af7b Francesconi, M. (Maria)|||/items/102d1263-2a4e-4bb3-a781-37f0df819b64 D’Andrea, L. (Laura)|||/items/fdc5db8f-0222-477a-bdee-c92d2fadd88a Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Colyn, L. (Leticia)|||/items/5972aa59-9877-442f-b405-1d4af39847db Fernández-Barrena, M.G. (Maite G.)|||/items/cfa77580-40b9-43a4-b237-b234ef7fb6cb Flammia, R.S. (Rocco Simone)|||/items/88a236d9-bd71-4050-a1b9-1645ca9ef09f Falchi, M. (Mario)|||/items/0e9e3a04-f8ea-43b6-af48-da4ddbe0aae0 Righi, D. (Daniela)|||/items/d332963f-65c8-4e85-8c8e-12ba45f625d0 Pedini, G. (Giorgia)|||/items/eeeeb8a5-e51f-4bcb-af23-b39951ef1054 Pantano, F. (Francesco)|||/items/8b8cffeb-f8a5-410f-b43d-ed67d4677a23 Bagni, C. (Claudia)|||/items/108ec5ce-f725-400f-a02f-2ae800d2dc79 Perrone, G. (Giuseppe)|||/items/902a6a22-bf18-40f4-a470-6ae8bc4a9ed9 Rana, R.A. (Rosa Alba)|||/items/a8822cf9-e765-4a21-924e-a6e2ef105b7d Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f Morini, S. (Sergio)|||/items/e5ce1f9e-6846-45ea-8583-6555829fbf10 Zalfa, F. (Francesca)|||/items/14da61f4-6c4a-41f6-ab47-c162a3474d60 |
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author |
| author2 |
Zingariello, M. (Maria)|||/items/b623e94b-bc53-4012-8f59-c257d6b8af7b Francesconi, M. (Maria)|||/items/102d1263-2a4e-4bb3-a781-37f0df819b64 D’Andrea, L. (Laura)|||/items/fdc5db8f-0222-477a-bdee-c92d2fadd88a Latasa, M.U. (María Ujué)|||/items/e1e74596-1598-4722-a96a-7bdd7cdec356 Colyn, L. (Leticia)|||/items/5972aa59-9877-442f-b405-1d4af39847db Fernández-Barrena, M.G. (Maite G.)|||/items/cfa77580-40b9-43a4-b237-b234ef7fb6cb Flammia, R.S. (Rocco Simone)|||/items/88a236d9-bd71-4050-a1b9-1645ca9ef09f Falchi, M. (Mario)|||/items/0e9e3a04-f8ea-43b6-af48-da4ddbe0aae0 Righi, D. (Daniela)|||/items/d332963f-65c8-4e85-8c8e-12ba45f625d0 Pedini, G. (Giorgia)|||/items/eeeeb8a5-e51f-4bcb-af23-b39951ef1054 Pantano, F. (Francesco)|||/items/8b8cffeb-f8a5-410f-b43d-ed67d4677a23 Bagni, C. (Claudia)|||/items/108ec5ce-f725-400f-a02f-2ae800d2dc79 Perrone, G. (Giuseppe)|||/items/902a6a22-bf18-40f4-a470-6ae8bc4a9ed9 Rana, R.A. (Rosa Alba)|||/items/a8822cf9-e765-4a21-924e-a6e2ef105b7d Avila, M.A. (Matías Antonio)|||/items/3ad9abbb-c18d-445b-86cf-cb76be15419f Morini, S. (Sergio)|||/items/e5ce1f9e-6846-45ea-8583-6555829fbf10 Zalfa, F. (Francesca)|||/items/14da61f4-6c4a-41f6-ab47-c162a3474d60 |
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author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Dadun. Depósito Académico Digital Universidad de Navarra |
| dc.subject.none.fl_str_mv |
Intrahepatic cholangiocarcinoma (iCCA) Fragile X mental retardation protein (FMRP) Cancers |
| topic |
Intrahepatic cholangiocarcinoma (iCCA) Fragile X mental retardation protein (FMRP) Cancers |
| description |
Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy of the intrahepatic biliary tract with a very poor prognosis. Although some clinicopathological parameters can be prognostic factors for iCCA, the molecular prognostic markers and potential mechanisms of iCCA have not been well investigated. Here, we report that the Fragile X mental retardation protein (FMRP), a RNA binding protein functionally absent in patients with the Fragile X syndrome (FXS) and also involved in several types of cancers, is overexpressed in human iCCA and its expression is significantly increased in iCCA metastatic tissues. The silencing of FMRP in metastatic iCCA cell lines affects cell migration and invasion, suggesting a role of FMRP in iCCA progression. Moreover, we show evidence that FMRP is localized at the invasive front of human iCCA neoplastic nests and in pseudopodia and invadopodia protrusions of migrating and invading iCCA cancer cells. Here FMRP binds several mRNAs encoding key proteins involved in the formation and/or function of these protrusions. In particular, we find that FMRP binds to and regulates the expression of Cortactin, a critical regulator of invadopodia formation. Altogether, our findings suggest that FMRP could promote cell invasiveness modulating membrane plasticity and invadopodia formation at the leading edges of invading iCCA cells. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2021-01-01 2021 2021-01-01 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10171/114702 |
| url |
https://hdl.handle.net/10171/114702 |
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Inglés eng |
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Inglés |
| language |
eng |
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open access http://purl.org/coar/access_right/c_abf2 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
MacMillan Press |
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MacMillan Press |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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1869411197726490624 |
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15,811543 |