Mehta, Rushabh: SOX4 and SMARCA4 as Cell Cycle Regulators of Triple Negative Breast Cancer
Title: SOX4 and SMARCA4 as Cell Cycle Regulators of Triple Negative Breast Cancer
Name: Rushabh Mehta
School affiliation: School of Arts and Sciences
Programs: Human Genetics Institute of New Jersey MacMillan Cancer Genetics Summer Undergraduate Research Fellowship (HGI-SURF)
Other contributors: Michael Gatza and Gaurav Mehta
Abstract: Triple negative breast cancer (TNBC) remains a leading cause of cancer deaths amongst women in the United States due to a distinct lack of targeted therapies as well as the aggressive behavior of the cancer. BRG1, the ATPase subunit of the SWI/SNF human chromatin remodeling complex, is overexpressed in approximately 90% of TNBC tumors and has been shown to contribute to tumor development and progression; however, the mechanisms by which BRG1 mediates these processes and the required cofactors remain unknown3. Recent work by the Gatza lab has determined that BRG1 interacts with the oncogenic transcription factor SOX4 and that this complex is responsible for regulating PI3K signaling in this subset of tumors. To better understand the downstream effects of BRG1-SOX4 signaling in TNBC, the large-scale tumor datasets produced by The Cancer Genome Atlas (TCGA) Program as well as the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) study were interrogated. Basal-like breast tumors, a molecularly identified subtype of breast cancer that is largely synonymous with TNBC1, will be investigated using these datasets. Overall, the in silico analysis reveals distinct signaling pathways active in tumors with gene expression differentially correlated with SOX4 and SMARCA4. Genomic as well as proteomic analysis provide the foundation for the assertion that SOX4 and SMARCA4 cooperate to promote cell proliferation through the downstream transcriptional control of cell cycle genes.