Targeting insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in metastatic melanoma to increase efficacy of BRAFV600E inhibitors
Autor: | Mark R. Albertini, Tae Won Kim, Yaohui G. Xu, Thomas C. Havighurst, Vladimir S. Spiegelman, Kyung Mann Kim |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Proto-Oncogene Proteins B-raf Cancer Research medicine.medical_treatment RNA-binding protein CRD-BP Article Targeted therapy 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Humans Molecular Biology neoplasms Melanoma Protein Kinase Inhibitors Gene knockdown biology Growth factor RNA-Binding Proteins medicine.disease Up-Regulation Gene Expression Regulation Neoplastic 030104 developmental biology Vemurafenib Drug Resistance Neoplasm 030220 oncology & carcinogenesis Insulin-like growth factor 2 Mutation biology.protein Cancer research Skin cancer |
Popis: | Melanoma is one of the deadliest forms of skin cancer. Although BRAF inhibitors significantly enhance survival of metastatic melanoma patients, most patients relapse after less than a year of treatment. We previously reported that mRNA binding protein Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is overexpressed in metastatic melanoma and that expression of IGF2BP1 confers resistance to chemotherapeutic agents. Here we demonstrate that IGF2BP1 plays an important role in the sensitivity of melanoma to targeted therapy. Inhibition of IGF2BP1 enhances the effects of BRAF-inhibitor and BRAF-MEK inhibitors in BRAF(V600E) melanoma. Also, knockdown of IGF2BP1 alone is sufficient to reduce tumorigenic characteristics in vemurafenib-resistant melanoma. These findings suggest that IGF2BP1 can be a novel therapeutic target for melanoma. |
Databáze: | OpenAIRE |
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