Inactivation of beta1 integrin induces proteasomal degradation of Myc oncoproteins
| العنوان: | Inactivation of beta1 integrin induces proteasomal degradation of Myc oncoproteins |
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| المؤلفون: | Sana Yokoi, Yusuke Suenaga, Tatsufumi Asayama, Shunsuke Sakai, Fumio Fukai, Manabu Sasada, Yoichiro Isohama, Hiroaki Kodama, Takuya Iyoda, Naoya Kase |
| المصدر: | Oncotarget Scopus-Elsevier |
| بيانات النشر: | Impact Journals LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, proteasomal degradation, integrin, Integrin, Peptide, Myc, 03 medical and health sciences, neuroblastoma, 0302 clinical medicine, fibronectin, Neuroblastoma, Pancreatic cancer, medicine, Gene, chemistry.chemical_classification, biology, Beta1 Integrin, medicine.disease, Fibronectin, 030104 developmental biology, Oncology, Targeted drug delivery, chemistry, 030220 oncology & carcinogenesis, biology.protein, Cancer research, Research Paper |
| الوصف: | The MYC family oncogenes (MYC, MYCN, and MYCL) contribute to the genesis of many human cancers. Among them, amplification of the MYCN gene and over-expression of N-Myc protein are the most reliable risk factors in neuroblastoma patients. On the other hand, we previously found that a peptide derived from fibronectin, termed FNIII14, is capable of inducing functional inactivation in β1-integrins. Here, we demonstrate that inactivation of β1-integrin by FNIII14 induced proteasomal degradation in N-Myc of neuroblastoma cells with MYCN amplification. This N-Myc degradation by FNIII14 reduced the malignant properties, including the anchorage-independent proliferation and invasive migration, of neuroblastoma cells. An in vivo experiment using a mouse xenograft model showed that the administration of FNIII14 can inhibit tumor growth, and concomitantly a remarkable decrease in N-Myc levels in tumor tissues. Of note, the activation of proteasomal degradation based on β1-integrin inactivation is applicable to another Myc family oncoprotein, c-myc, which also reverses cancer-associated properties in pancreatic cancer cells. Collectively, β1-integrin inactivation could be a new chemotherapeutic strategy for cancers with highly expressed Myc. FNIII14, which is a unique pharmacological agent able to induce β1-integrin inactivation, may be a promising drug targeting Myc oncoproteins for cancer chemotherapy. |
| اللغة: | English |
| تدمد: | 1949-2553 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8ee5b855c355aa7857aab4ce4a607342 http://europepmc.org/articles/PMC6697639 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....8ee5b855c355aa7857aab4ce4a607342 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19492553 |
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