The large GTPase, mGBP-2, regulates Rho family GTPases to inhibit migration and invadosome formation in Triple-Negative Breast Cancer cells.

Abstract

Breast cancer is the most common cancer in women. Despite advances in early detection and treatment, it is predicted that over 40,000 women will die of breast cancer in 2019. This number of women is still too high. To lower this number, more information about the molecular players in breast cancer are needed. Several members of the Guanylate-Binding Proteins (GBPs) have been correlated with better prognosis in breast cancer. In this study, we asked if the expression of GBP-2 in breast cancer merely provided a biomarker for improved prognosis or whether it actually contributed to improving outcome. Specifically, we asked whether murine GBP-2 exhibited cell autonomous behavior that altered breast cancer cells in a manner predicted to improve prognosis. To answer this, the 4T1 model of murine Triple-Negative Breast Cancer was used. 4T1 cells themselves are highly aggressive and highly metastatic, while 67NR cells, isolated from the same tumor, do not leave the primary site. mGBP-2 did not alter cell proliferation in these two cell lines, but mGBP-2 expression inversely correlated with migration. More specifically, mGBP-2 inhibits cell migration and invadopodia formation by inhibiting the activation of Rac1, while promoting the activation of CDC42 and RhoA. Together these data demonstrate that mGBP-2 is responsible for cell autonomous activities that make breast cancer cells less aggressive.