Luke Bass
Luke Bass
Helios Scholar
School: Lewis and Clark College
Hometown: Chandler, Arizona
Mentor: Emily Tsutsumi, PhD
PI: Suwon Kim, PhD 

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GNG1 knockout increases ING4-deleted TNBC cell proliferation

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that leads to worse patient survival compared to other breast cancer subtypes. There are few treatments available for TNBC. The molecular mechanisms of TNBC metastasis are not well understood. The tumor suppressor Inhibitor of Growth 4 (ING4) has been shown to be downregulated in 16-34% of breast tumors and is associated with poorer patient outcome. Previously, it has been shown that inhibiting the Gβγ subunit decreased Cxcl10-induced migration of ING4-deleted TNBC cells, indicating that the Cxcr3 G-protein pathway is required for migration. GNG1 encodes for the Gγ1 subunit that has been shown to be upregulated in lung cancer. However, the role of GNG1 in TNBC is not known.


Gene expression analysis from the METABRIC dataset suggested that GNG1 may be a secondary tumor suppressor in TNBC. To test if GNG1 affects proliferation of ING4-deleted TNBC cells, sulforhodamine B (SRB) assays were performed in the presence and absence of Cxcl10. The results showed that GNG1 knockout increased cell proliferation in the presence of Cxcl10, indicating that GNG1 indirectly inhibits proliferation of ING4-deficient TNBC cells in the presence of Cxcl10. Cxcl10-induced migration was assessed in the GNG1 knockout cells using transwell migration assays. Compared to the vector control, two out of three GNG1 knockout cells showed no change in migration when treated with Cxcl10, indicating that GNG1 does not directly participate in Cxcl10-induced migration. Further experimentation will be needed to pinpoint the effects of GNG1 knockout on cell proliferation and Cxcl10-induced migration as well as locate which GNG gene encodes for the γ subunit that directly participates in the Cxcl10/Cxcr3 signaling pathway.