Transfer of metastatic traits via miR‐200c in extracellular vesicles derived from colorectal cancer stem cells is inhibited by atractylenolide I
| Autor: | Jialiang Ying, Tian Xie, Xiaofen Xu, Dongxin Tang, Gang Cao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Medicine (General) Cell atractylenolide I Medicine (miscellaneous) medicine.disease_cause Metastasis 03 medical and health sciences stemness R5-920 0302 clinical medicine Cancer stem cell microRNA medicine metastasis Protein kinase B PI3K/AKT/mTOR pathway Research Articles Chemistry medicine.disease 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Molecular Medicine Stem cell PI3K/Akt/mTOR Carcinogenesis extracellular vesicles Research Article |
| Zdroj: | Clinical and Translational Medicine Clinical and Translational Medicine, Vol 10, Iss 4, Pp n/a-n/a (2020) |
| ISSN: | 2001-1326 |
| Popis: | Cancer stem cells (CSCs) are important factors contributing to tumorigenesis. We examined whether CSCs isolated from colorectal cancer (CRC) cells possess metastatic properties that can be transferred to non‐CSCs via the delivery of miR‐200c enclosed in extracellular vesicles (EVs). The inhibitory effect of atractylenolide I (ATL‐1), a traditional Chinese medicinal compound, on miR‐200c activity and metastatic transfer was investigated. EVs were isolated from colorectal CSCs. The expression of miR‐200c was evaluated in CSCs and CSC‐derived EVs, and horizontal transfer of metastatic properties via EVs to non‐CSCs was investigated in terms of cell behavior and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling. CSCs isolated from metastatic CRC cells exhibited higher levels of miR‐200c than those in nonmetastatic CRC cells. Overexpression of miR‐200c in CSCs enhanced metastatic potential by promoting proliferation and inhibiting apoptosis, in turn leading to the release of EVs carrying an excess of miR‐200c. Non‐CSCs co‐cultured with miR‐200c‐containing EVs exhibited enhanced invasion and stemness maintenance associated with PI3K/Akt/mTOR activation, demonstrating successful metastatic transfer via EV delivery. Furthermore, ATL‐1 impaired the EV‐mediated transfer of metastatic properties by suppressing miR‐200c activity and disrupting EV uptake by non‐CSCs. EVs are critical signal transducers that facilitate intercellular communication and exchange of metastatic properties, which can be controlled by ATL‐1. The findings are useful in the development of microRNA‐based anticancer strategies by targeting EV‐mediated activity, especially using natural compounds. A key factor that contributes to colorectal tumour metastasis is the production of a large number of CSCs in the tumour microenvironment. These CSCs secrete EVs that act as carrier vehicles to transport miR‐200c, which regulates stemness maintenance in CRC cells and promotes CRC metastasis. Horizontal transfer of miR‐200c‐mediated properties is facilitated via the co‐culture of CRC cells and miR‐200c‐containing EVs, and the uptake of EVs by CRC cells results in increased metastatic potential, enhanced stem‐like traits, and activation of PI3K/AKT/mTOR signalling. ATL‐1 suppresses the activity of CSCs while inhibiting the uptake of EVs by CRC cells to prevent metastasis. |
| Databáze: | OpenAIRE |
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