Cross-talk of EGF and IGF-1 signaling promotes EMT gene expression: Implications for morphology and proliferation in breast cancer cells

Abstract

Abstract Breast cancer (BC) is a significant cause of mortality associated with cancer, presenting a substantial risk to women's health and overall welfare on a global scale. Despite notable progress in BC treatment, the prognosis for metastatic BC remains unfavorable, ultimately leading to fatality. To develop advanced therapeutic approaches, it is imperative to have a comprehensive comprehension of the underlying process responsible for the systemic dispersion of cancer cells. Numerous experimental findings indicate that an epithelial-to-mesenchymal transition (EMT) is essential in the intricate progression of metastasis formation. EMT is a crucial initial stage observed in certain highly aggressive malignancies, such as breast cancer, facilitating the processes of invasion and metastasis. The current study assessed the impact of epidermal growth factor (EGF) and insulin-like growth factor (IGF-1) on breast cell lines, specifically MDA-MB-468, MDA-MB-231, and MCF10A. The experimental techniques employed in this study were qPCR, western blotting, and subsequent investigation of gene-gene interactions. Cell migration and proliferation assays were also conducted to investigate the following impacts of EGF and IGF-1 on breast cells. A study revealed that IGF-1 can augment EMT induced by EGF. Furthermore, it was observed that the expression levels of EMT-inducing transcription factors, namely snail, slug, zeb1, and zeb2, were increased in breast cells that were treated with EGF or IGF-1. Furthermore, it was observed that the stimulation of cell proliferation in metastatic BC cell lines is significantly enhanced upon administration of EGF and IGF-1. Notably, the observed augmentation in cellular proliferation was not discernible in non-malignant breast cells. Additionally, it was revealed that the morphology of BC cell lines undergoes alterations upon exposure to EGF and IGF-1. In contrast, it has been observed that the shape of normal BC stays unaltered, suggesting that the stimulation of EMT in breast tumor cells is induced explicitly by growth factors such as EGF and IGF-1. These research findings indicate that incorporating EGFR/IGF-R signaling as a potential therapeutic target, in conjunction with conventional treatment methods, exhibits substantial potential in attenuating tumor growth and progression, prolonging the overall survival rates of cancer patients.