GROα overexpression drives cell migration and invasion in triple negative breast cancer cells

Triple negative breast cancer (TNBC) is a subtype of highly aggressive breast cancer with poor prognosis. The main characteristic feature of TNBC is its lack of expression of ER, PR and HER2 receptors that are targets for treatments. Hence, it is imperative to identify novel therapeutic strategies to target TNBC. Our aim was to examine whether GRO alpha is a specific marker for TNBC metastasis. For this we performed qPCR, ELISA, migration/invasion assays, western blotting, and siRNA transfections. Evaluation of baseline GRO alpha expression in different breast cancer (BC) subtypes showed that it is significantly upregulated in breast tumor cells, specifically in TNBC cell line. On further evaluation in additional 17 TNBC cell lines we found that baseline GRO alpha expression was significantly elevated in >50% of the cell lines validating GRO alpha overexpression specifically in TNBC cells. Moreover, GRO alpha-stimulation in MCF7 and SKBR3 cells and GRO alpha-knockdown in MDA-MB-231 and HCC1937 cells elicited dramatic changes in migration and invasion abilities in vitro. Corresponding changes in EMT markers were also observed in phenotypically modified BC cells. Furthermore, mechanistic studies identified GRO alpha regulating EMT markers and migration/invasion via MAPK pathway and specific inhibition using PD98059 resulted in the reversal of effects induced by GRO alpha on BC cells. In conclusion, our study provides strong evidence to suggest that GRO alpha is a critical modulator of TNBC migration/invasion and proposes GRO alpha as a potential therapeutic target for treatment of TNBC metastasis.