The Role of Akt/Rab۵A Signalling in Regulating Cell Migration of MDA-MB-۲۳۱ Breast Cancer Cell Line

Rab۵A and Akt pathways are reported to be responsible for the invasiveness of cancer cells, indicated by the fact that Rab۵A activates the downstream Phosphoinositide-۳-kinases (PI۳K)/Akt signalling pathway, which results in promoting cancer metastasis. However, little attention has been given to the emerging role of Rab۵A and Akt signalling pathways in regulating the direction of MDA-MB-۲۳۱ cell migration. MDA-MB-۲۳۱ breast cancer cell line was used as a model in this study because it is highly metastatic and motile. Time-lapse microscopy was used to examine the effect of Akt and Rab۵A inhibitors on cell migration, proliferation and wound healing. Later, the cells were transfected with GFP-Akt-PH or GFP-Rab۵A (used as a biosensor to detect Akt and Rab۵A). Therefore, confocal time-lapse images were used to visualize Akt and Rab۵A at the front and rear edges of the cells. The recorded data demonstrated that Akt and Rab۵A inhibition reduced cell migration, proliferation and wound healing. The results of the current study also demonstrated that Akt localizes at the trailing edge while Rab۵A localize more at the leading edge than the trailing edge of cells. This study suggests that Akt and Rab۵A inhibition might regulate the direction of breast cancer migration.

Keywords:

Akt , Rab۵A , cancer cell migration , MDA-MB-۲۳۱ cell line