Academic Journal
CDH6‐activated αIIbβ3 crosstalks with α2β1 to trigger cellular adhesion and invasion in metastatic ovarian and renal cancers ; Running title: Integrin crosstalk in ovarian and renal carcinomas
| العنوان: | CDH6‐activated αIIbβ3 crosstalks with α2β1 to trigger cellular adhesion and invasion in metastatic ovarian and renal cancers ; Running title: Integrin crosstalk in ovarian and renal carcinomas |
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| المؤلفون: | Bartolomé, Rubén Álvaro, Robles, Javier, Martin-Regalado, Ángela, Pintado-Berninches, Laura, Burdiel, Miranda, Jaén, Marta, Aizpurua, Carmen, Imbaud, Juan Ignacio, Casal, J. Ignacio |
| المساهمون: | Ministerio de Ciencia e Innovación (España), Bartolomé, Rubén Álvaro, Martin-Regalado, Ángela, Pintado-Berninches, Laura, Burdiel, Miranda, Jaén, Marta, Imbaud, Juan Ignacio, Casal, J. Ignacio |
| بيانات النشر: | John Wiley & Sons |
| سنة النشر: | 2021 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | CDH6, α2β1 integrin, Ovarian and renal cancer, Metastasis, Platelets |
| الوصف: | 17 p.-7 fig. ; Cadherin 6 (CDH6) is significantly overexpressed in advanced ovarian and renal cancers. However, the role of CDH6 in cancer metastasis is largely unclear. Here, we investigated the impact of CDH6 expression on integrin‐mediated metastatic progression. CDH6 preferentially bound to αIIbβ3 integrin, a platelet receptor scarcely expressed in cancer cells, and this interaction was mediated through the cadherin RGD motif. Furthermore, CDH6 and CDH17 were found to interact with α2β1 in αIIbβ3low cells. Transient silencing of CDH6, ITGA2B or ITGB3 genes caused a significant loss of proliferation, adhesion, invasion and lung colonization through the downregulation of SRC, FAK, AKT and ERK signaling. Interaction of αIIbβ3 with CDH6, and subsequent αIIbβ3 activation, promoted activation of α2β1 and cell adhesion in ovarian and renal cancer cells. Additionally, monoclonal antibodies specific to the cadherin RGD motif and clinically‐approved αIIbβ3 inhibitors could block pro‐metastatic activity in ovarian and renal tumors. In summary, the interaction between CDH6 and αIIbβ3 regulate α2β1‐mediated adhesion and invasion of ovarian and renal cancer metastatic cells, and constitutes a therapeutic target of broad potential for treating metastatic progression. ; This research was supported by grants from the Ministerio de Ciencia e Innovación (Spain) (RTC2017-2017-6260-1 and RTI2018-095055-B-100). ; Peer reviewed |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1574-7891 |
| Relation: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTC2017-2017-6260-1; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-095055-B-100; Publisher's version; https://doi.org/10.1002/1878-0261.12947; Sí; Molecular Oncology (2021); http://hdl.handle.net/10261/235244; http://dx.doi.org/10.13039/501100004837 |
| DOI: | 10.1002/1878-0261.12947 |
| DOI: | 10.13039/501100004837 |
| الاتاحة: | http://hdl.handle.net/10261/235244 https://doi.org/10.1002/1878-0261.12947 https://doi.org/10.13039/501100004837 |
| Rights: | open |
| رقم الانضمام: | edsbas.8E4B4244 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15747891 |
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| DOI: | 10.1002/1878-0261.12947 |