FOSL1 promotes stem celllike characteristics and anoikis resistance to facilitate tumorigenesis and metastasis in osteosarcoma by targeting SOX2.
Int J Mol Med
; 54(5)2024 11.
Article
in En
| MEDLINE
| ID: mdl-39219279
ABSTRACT
Metastasis is the leading cause of cancerrelated death in osteosarcoma (OS). OS stem cells (OSCs) and anoikis resistance are considered to be essential for tumor metastasis formation. However, the underlying mechanisms involved in the maintenance of a stemcell phenotype and anoikis resistance in OS are mostly unknown. Foslike antigen 1 (FOSL1) is important in maintaining a stemlike phenotype in various cancers; however, its role in OSCs and anoikis resistance remains unclear. In the present study, the dynamic expression patterns of FOSL1 were investigated during the acquisition of cancer stemlike properties using RNA sequencing, PCR, western blotting and immunofluorescence. Flow cytometry, tumorsphere formation, clone formation assays, anoikis assays, western blotting and in vivo xenograft and metastasis models were used to further investigate the responses of the stemcell phenotype and anoikis resistance to FOSL1 overexpression or silencing in OS cell lines. The underlying molecular mechanisms were evaluated, focusing on whether SOX2 is crucially involved in FOSL1mediated stemness and anoikis in OS. FOSL1 expression was observed to be upregulated in OSCs and promoted tumorsphere formation, clone formation and tumorigenesis in OS cells. FOSL1 expression correlated positively with the expression of stemnessrelated factors (SOX2, NANOG, CD117 and Stro1). Moreover, FOSL1 facilitated OS cell anoikis resistance and promoted metastases by regulating the expression of apoptosis related proteins BCL2 and BAX. Mechanistically, FOSL1 upregulated SOX2 expression by interacting with the SOX2 promoter and activating its transcription. The results also showed that SOX2 is critical for FOSL1mediated stemlike properties and anoikis resistance. The current findings indicated that FOSL1 is an important regulator that promotes a stem celllike phenotype and anoikis resistance to facilitate tumorigenesis and metastasis in OS by regulating the transcription of SOX2. Thus, FOSL1 might represent an attractive target for therapeutic interventions in OS.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neoplastic Stem Cells
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Osteosarcoma
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Gene Expression Regulation, Neoplastic
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Proto-Oncogene Proteins c-fos
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Anoikis
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SOXB1 Transcription Factors
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Carcinogenesis
Limits:
Animals
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Female
/
Humans
/
Male
Language:
En
Journal:
Int J Mol Med
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2024
Document type:
Article
Country of publication: