Keilen Costilla Martinez
Keilen Costilla Martinez
Keilen Costilla Martinez
Helios Scholar
School: Smith College
Hometown: Phoenix, Arizona
Mentor: Suwon Kim, Ph.D.
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ING4’s Contribution to the Inhibition of CXCL10 Induced Migration in Triple Negative Breast Cancer Cell Line MDA-mb-46

Triple negative breast cancer (TNBC) accounts for 15-20% of all breast cancer. This subtype is characterized by being estrogen receptor (ER), progesterone receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2) negative. Compared to the other breast cancer subtypes, TNBC has the highest recurrence percentage (50%) over 15 years and a higher mortality rate. Previous research shows that ING4 functions as a tumor suppressor that inhibits NF-kB, a central molecule that mediates immune response by activating gene transcription. One of NF-kB’s target genes is CXCL10, a signaling protein that promotes chemotaxis in immune cells and that is associated with aggressive breast cancer. 

In TNBC cell line MDA-mb-468, we hypothesized that CXCL10 might induce migration. In order to test for a migration phenotype, a migration assay was employed using Boyden chambers. Cells were left to set in the Boyden chambers and were treated with and without CXCL10. The results show that migration does occur, but only in the ING4 knockout cell line, V2H1. The mechanism for CXCL10 is unknown, but we hypothesized that the migration phenotype (seen in cells lacking ING4) could be caused by the transactivation of Epidermal Growth Factor Receptor (EGFR), mediated by CXCL10’s G-coupled protein receptor CXCR3. To see whether CXCL10 induced phosphorylation of EGFR in the absence of ING4, a western blot was performed with lysates prepared from ING4 CRISPR constructs in MDA-mb-468 cells and treated with CXCL10. The western blot shows that knocking out ING4 does not increase phosphorylation of EGFR. Taken together, we conclude that  ING4 contributes to inhibition of CXCL10-induced migration and that without ING4, cells migrate in the presence of CXCL10.