GNG2 gene does not affect proliferation or Cxcl10-induced migration of ING4-deleted breast cancer cells
Triple negative breast cancer (TNBC) is more metastatic compared to other breast cancer subtypes. Because metastatic TNBC has limited treatment options, the 5-year survival of patients is 12%. Our research aims to develop treatments to reduce TNBC metastasis. The chemokine Cxcl10 has been shown to induce migration of tumor suppressor Inhibitor of Growth 4 (ING4)-deleted cells through the Cxcr3 receptor. Inhibition of the Cxcr3 G protein βγ subunit blocked migration, indicating that the Gβγ subunit is critical. Previous studies suggested a Gγ gene, G Protein Subunit Gamma 2 (GNG2), is a tumor suppressor. GNG2 involvement in Cxcl10-signaled migration is unknown.
To assess the role of GNG2 in TNBC patient outcome, we performed gene expression analyses of GNG2 and ING4 in the METABRIC dataset. GNG2 was not correlated to disease-free survival, indicating GNG2 did not affect TNBC aggressiveness. To see a possible relationship between GNG2 and ING4, we correlated the genes to patient outcome. Patients with ING4 low tumors had worse outcome regardless of GNG2 expression. These results indicated that low ING4 expression correlated to aggressive TNBC, but GNG2 did not. GNG2 was knocked-out in ING4-deficient TNBC MDA-MB-231 cells to evaluate cancer phenotypes with/without Cxcl10 using proliferation and transwell migration assays. Results showed that GNG2 is not involved in proliferation. Migration results were inconclusive, meaning that GNG2 involvement in the Cxcl10/Cxcr3 pathway remains to be seen. Further studies will determine whether GNG2 is required for Cxcl10-signaled migration. Results of these studies will aid development of targeted treatment for ING4-deficient TNBC metastasis.
