Attenuation of malignant phenotypes of breast cancer cells through eIF2α-mediated downregulation of Rac1 signaling.

摘要: Blocking dephosphorylation of eukaryotic translation initiation factor 2α (eIF2α) is reported to alter proliferation and differentiation various cells. Using salubrinal guanabenz as an inhibitory agent eIF2α, we addressed a question whether elevated level phosphorylated eIF2α attenuates malignant phenotypes triple negative breast cancer cells (TNBCs) that lack estrogen receptor, progesterone receptor human epidermal growth receptor-2. We determined effects on in vitro phenotype 4T1 mammary tumor MDA-MB-231 evaluated their vivo using BALB/c mice injected with The results revealed these agents block the survival cells, well invasion motility. Silencing involved reduction Furthermore, salubrinal-driven inactivation Rac1 was suppressed treated siRNA, treatment siRNA reduced cell In vivo assay subcutaneous administration volume weight tumors induced by Collectively, indicate can attenuate through eIF2α-mediated pathway. Since are known inhibit bone resorption, this study provides potential use regulation suppressing metastasis cancer.