Siglec-15-induced autophagy promotes invasion and metastasis of human osteosarcoma cells by activating the epithelial–mesenchymal transition and Beclin-1/ATG14 pathway

Autor: Bingxin Zheng, Keliang Song, Lingling Sun, Yang Gao, Yan Qu, Chongmin Ren, Peng Yan, Wenfang Chen, Wei Guo, Chuanli Zhou, Bin Yue
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cell & Bioscience, Vol 12, Iss 1, Pp 1-15 (2022)
Druh dokumentu: article
ISSN: 2045-3701
DOI: 10.1186/s13578-022-00846-y
Popis: Abstract Background Pulmonary metastasis is the main cause of poor prognosis in osteosarcoma. Sialic acid-bound immunoglobulin lectin 15 (Siglec-15) has been demonstrated to be obviously correlated with pulmonary metastasis in osteosarcoma patients. However, the effect of Siglec-15 on autophagy in osteosarcoma remains unclear, while the role and mechanism of Siglec-15-related autophagy in lung metastasis also remain unknown. Methods The expression levels of Siglec-15 and Beclin-1 were detected in osteosarcoma tissues using immunohistochemistry (IHC). The effect of Siglec-15 on metastasis was investigated using Transwell, wound healing and animal experiments with osteosarcoma cells. Corresponding proteins were confirmed using Western blotting when Siglec-15 or Beclin-1 was silenced or overexpressed. Changes in autophagy and the cytoskeleton were detected using immunofluorescence and transmission electron microscopy. Results Siglec-15 and Beclin-1 expression was evaluated both in lung metastases and in patients who presented with pulmonary metastasis of osteosarcoma. Immunoprecipitation experiments revealed that Siglec-15 interacts directly with Beclin-1, an important autophagic protein. Moreover, loss of Siglec-15 distinctly inhibited autophagy and reduced Beclin-1/ATG14 expression. The decreased invasion and migration caused by Siglec-15 silencing could be reversed by Beclin-1 overexpression. Additionally, autophagy can promote the epithelial–mesenchymal transition (EMT) and affect cytoskeletal rearrangement, which was confirmed by overexpression or silencing of Beclin-1. Conclusions These findings confirmed the role of Siglec-15 in the regulation of autophagy and elaborated the relationship and mechanisms between autophagy and the metastasis of osteosarcoma cells.
Databáze: Directory of Open Access Journals
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