Rab22a-NeoF1 fusion protein promotes osteosarcoma lung metastasis through its secretion into exosomes
| Autor: | Xin Wang, Wenqiang Liu, Dan Liao, Kuntai Jiang, Tiebang Kang, Ruhua Zhang, Jingjing Li, Zhiliang Cao, Miao Li, Sui Jianhua, Cuiling Zeng, Yi Xin Zeng, Jingxuan Wang, Li Zhong |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Lung Neoplasms RHOA Oncogene Proteins Fusion lcsh:Medicine Exosomes Article Metastasis Mice 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Bone cancer Genetics medicine Animals Humans Secretion HSP90 Heat-Shock Proteins lcsh:QH301-705.5 Osteosarcoma biology Chemistry lcsh:R medicine.disease Fusion protein Microvesicles Gene Expression Regulation Neoplastic Focal Adhesion Kinase 2 RAW 264.7 Cells 030104 developmental biology lcsh:Biology (General) rab GTP-Binding Proteins 030220 oncology & carcinogenesis Cancer cell biology.protein STAT protein Cancer research rhoA GTP-Binding Protein Oligopeptides Protein Binding |
| Zdroj: | Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-16 (2021) Signal Transduction and Targeted Therapy |
| ISSN: | 2059-3635 |
| Popis: | It remains unknown for decades how some of the therapeutic fusion proteins positive in a small percentage of cancer cells account for patient outcome. Here, we report that osteosarcoma Rab22a-NeoF1 fusion protein, together with its binding partner PYK2, is sorted into exosomes by HSP90 via its KFERQ-like motif (RVLFLN142). The exosomal Rab22a-NeoF1 fusion protein facilitates the pulmonary pre-metastatic niche formation by recruiting bone marrow-derived macrophages. The exosomal PYK2 activates RhoA in its negative recipient osteosarcoma cells and induces signal transducer and activator of transcription 3 activation in its recipient macrophages to increase M2 phenotype. Consequently, lung metastases of its recipient osteosarcoma cells are promoted by this exosomal Rab22a-NeoF1 fusion protein, and this event can be targeted by disrupting its interaction with PYK2 using a designed internalizing RGD peptide. |
| Databáze: | OpenAIRE |
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