دورية أكاديمية
Autocrine signaling of NRP1 ligand galectin-1 elicits resistance to BRAF-targeted therapy in melanoma cells
| العنوان: | Autocrine signaling of NRP1 ligand galectin-1 elicits resistance to BRAF-targeted therapy in melanoma cells |
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| المؤلفون: | Rizzolio S., Corso S., Giordano S., Tamagnone L. |
| المساهمون: | Rizzolio S., Corso S., Giordano S., Tamagnone L. |
| سنة النشر: | 2020 |
| المجموعة: | Università degli studi di Torino: AperTo (Archivio Istituzionale ad Accesso Aperto) |
| مصطلحات موضوعية: | Autocrine signaling, Braf, Cancer therapy, Cell signaling, Egfr, Galectin, Melanoma, Molecular biology, Neuropilin, Oncogenic signaling |
| الوصف: | Melanoma cells addicted to mutated BRAF oncogene activity can be targeted by specific kinase inhibitors until they develop resistance to therapy.We observed that the expression of Galectin-1 (Gal-1), a soluble ligand of Neuropilin-1 (NRP1), is upregulated in melanoma tumor samples and melanoma cells resistant to BRAF-targeted therapy. We then demonstrated that Gal-1 is a novel driver of resistance to BRAF inhibitors in melanoma and that its activity is linked to the concomitant upregulation of the NRP1 receptor observed in drug-resistant cells. Mechanistically, Gal-1 sustains increased expression of NRP1 and EGFR in drug-resistant melanoma cells. Moreover, consistent with its role as a NRP1 ligand, Gal-1 negatively controls p27 levels, a mechanism previously found to enable EGFR upregulation in cancer cells. Finally, the combined treatment with a Gal-1 inhibitor and a NRP1 blocking drug enabled resistant melanoma cell resensitization to BRAF-targeted therapy. In summary, we found that the activation of Galectin-1/NRP1 autocrine signaling is a new mechanism conferring independence from BRAF kinase activity to oncogene-addicted melanoma cells. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32784465; info:eu-repo/semantics/altIdentifier/wos/WOS:000578985200001; volume:12; issue:8; firstpage:1; lastpage:14; numberofpages:14; journal:CANCERS; http://hdl.handle.net/2318/1799551Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85090604159 |
| DOI: | 10.3390/cancers12082218 |
| الإتاحة: | https://doi.org/10.3390/cancers12082218Test http://hdl.handle.net/2318/1799551Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.E90067E9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cancers12082218 |
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