Circulating Small Extracellular Vesicles Activate TYRO3 to Drive Cancer Metastasis and Chemoresistance
- Title
- Circulating Small Extracellular Vesicles Activate TYRO3 to Drive Cancer Metastasis and Chemoresistance
- Author
- 김진기
- Issue Date
- 2021-07
- Publisher
- AMER ASSOC CANCER RESEARCH
- Citation
- CANCER RESEARCH, v. 81, NO 13, Page. 3539-3553
- Abstract
- Extracellular vesicles (EV) in the tumor microenvironment
have emerged as crucial mediators that promote proliferation,
metastasis, and chemoresistance. However, the role of circulating
small EVs (csEV) in cancer progression remains poorly understood. In this study, we report that csEV facilitate cancer progression and determine its molecular mechanism. csEVs strongly
promoted the migration of cancer cells via interaction with
phosphatidylserine of csEVs. Among the three TAM receptors,
TYRO3, AXL, and MerTK, TYRO3 mainly interacted with
csEVs. csEV-mediated TYRO3 activation promoted migration
and metastasis via the epithelial–mesenchymal transition and
stimulation of RhoA in invasive cancer cells. Additionally,
csEV–TYRO3 interaction induced YAP activation, which led to
increased cell proliferation and chemoresistance. Combination
treatment with gefitinib and KRCT-6j, a selective TYRO3 inhibitor, significantly reduced tumor volume in xenografts implanted with gefitinib-resistant non–small cell lung cancer cells. The
results of this study show that TYRO3 activation by csEVs
facilitates cancer cell migration and chemoresistance by activation of RhoA or YAP, indicating that the csEV/TYRO3 interaction may serve as a potential therapeutic target for aggressive
cancers in the clinic.
- URI
- https://aacrjournals.org/cancerres/article/81/13/3539/666854/Circulating-Small-Extracellular-Vesicles-Activatehttps://repository.hanyang.ac.kr/handle/20.500.11754/172591
- ISSN
- 00085472; 15387445
- DOI
- 10.1158/0008-5472.CAN-20-3320
- Appears in Collections:
- COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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