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- Title
Rab22a-NeoF1 fusion protein promotes osteosarcoma lung metastasis through its secretion into exosomes.
- Authors
Zhong, Li; Liao, Dan; Li, Jingjing; Liu, Wenqiang; Wang, Jingxuan; Zeng, Cuiling; Wang, Xin; Cao, Zhiliang; Zhang, Ruhua; Li, Miao; Jiang, Kuntai; Zeng, Yi-Xin; Sui, Jianhua; Kang, Tiebang
- Abstract
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.
- Publication
Signal Transduction & Targeted Therapy, 2021, Vol 6, Issue 1, p1
- ISSN
2095-9907
- Publication type
Article
- DOI
10.1038/s41392-020-00414-1