SphK1 functions downstream of IGF-1 to modulate IGF-1-induced EMT, migration and paclitaxel resistance of A549 cells: A preliminary in vitro study

Insulin-like growth factor-1 (IGF-1) -induced epithelial-mesenchymal transition (EMT) plays a key role in the metastasis and drug resistance of non-small cell lung cancer (NSCLC). Sphingosine kinase-1 (SphK1) is also involved in EMT of NSCLC. However, the interaction between SphK1 and IGF-1 in the EMT of NSCLC is largely unknown. To clarify this issue, we examined the involvement of SphK1 in IGF-1-induced EMT using human lung cancer cell line A549, and its paclitaxel-resistant subline. Cell viability was evaluated by cell counting kit-8 assay; Migratory ability was examined using scratch wound healing test; Protein expression levels of SphK1, vimentin, fibronectin, N-cadherin and E-cadherin were detected by western blot analysis, respectively. The results showed that, IGF-1 treatment of A549 cells stimulated the expression of SphK1, the activation of ERK and AKT, the cell migration, and the expression of EMT hallmark proteins, while inhibition of SphK1 by its specific inhibitor SKI-II suppressed all the above changes and increased the sensitivity of A549 cells to paclitaxel. Our data demonstrate that SphK1 acts as a downstream effector of IGF-1 and plays a critical role in IGF-1-induced EMT, cell migration and paclitaxel resistance of A549 cells, suggesting that SphK1 might be a potential therapeutic target for NSCLC.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research

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