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- Title
Siglec-15-induced autophagy promotes invasion and metastasis of human osteosarcoma cells by activating the epithelial–mesenchymal transition and Beclin-1/ATG14 pathway.
- Authors
Zheng, Bingxin; Song, Keliang; Sun, Lingling; Gao, Yang; Qu, Yan; Ren, Chongmin; Yan, Peng; Chen, Wenfang; Guo, Wei; Zhou, Chuanli; Yue, Bin
- 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.
- Subjects
EPITHELIAL-mesenchymal transition; OSTEOSARCOMA; METASTASIS; TRANSMISSION electron microscopy
- Publication
Cell & Bioscience, 2022, Vol 12, Issue 1, p1
- ISSN
2045-3701
- Publication type
Article
- DOI
10.1186/s13578-022-00846-y