Fibronectin 1 promotes melanoma proliferation and metastasis by inhibiting apoptosis and regulating EMT

Background and aims: The complex process of cancer metastasis remains the least understood. Tumor cells alter their protein expression profile to survive from the tumor metastasis. Fibronectin 1 (FN1 gene coding protein) is a member of the glycoprotein family that has been shown to play an important role in cancer metastasis. However, its effects on melanoma metastasis are still unclear. Methods: We detected the FN1 expression between metastatic cells and primary cells by using Western blot and RT-qPCR assays. And, we analyzed the expressed feature of FN1 in different tissues and examined the clinical relevance of upregulated FN1 in melanoma progression by bioinformatic analysis. Furthermore, we downregulated the expression of FN1 by small interfering RNA technique to reveal the effect of FN1 on melanoma phenotype and expression of related genes. Finally, we used bioinformatics to reveal the possible mechanism of FN1 regulating melanoma progression. Results: We reported that the expression of FN1 was changed during melanoma metastasis. In this study, we established two metastatic cell lines of melanoma through mouse model, and found that metastatic cells exhibited stronger mesenchyme phenotype and possessed higher FN1 expression level compared to primary cells. Besides, we examined the clinical relevance of upregulated FN1 in tumor progression. Small interfering RNA (siRNA)-mediated downregulation of FN1 suppressed the migration, invasion, adhesion, proliferation capabilities and induced apoptosis of melanoma cells. We detected a diminished EMT-related gene signature including increased expression of E-cadherin and decreased expression of N-cadherin and Vimentin. Downregulation of FN1 also increased Bax/Bcl-2 ratio which might result in apoptosis of melanoma cells. Bioinformatics analysis revealed that FN1 most likely involved in focal adhesion and PI3K-Akt signaling pathway to regulate EMT process and apoptosis. Conclusions: Taken together, these findings demonstrated a role of FN1 in promoting melanoma metastasis by inhibiting apoptosis and regulating EMT.