SOX4 and SMARCA4 cooperatively regulate PI3K signaling through transcriptional activation OF TGFBR2 in triple negative breast cancer

Genomic and proteomic analyses coupled withmechanistic studies identified TGFBR2as a direct transcriptional target of SOX4and demonstrated that TGFBR2 is required to mediate SOX4-dependent PI3K signaling. We further reportthat SOX4 and the SWI/SNF ATPase SMARCA4, which are uniformly overexpressed in basal-like tumors,form a previously unreported complex that is requiredto maintain an open chromatin conformationat the TGFBR2regulatory regionsin order tomediateTGFBR2expressionand PI3K signaling. Total RNA was extracted from HCC1143 cells treated with either siRNA targeting SOX4 or non-targeting control siRNA for 96 hours. RNA libraries were prepared using theNuGen Ovation Universal RNA-Seq System (Catalog # 0343-32)and paired end (2x48bp) sequencing was performed usingthe Illumina NextSeq system. Paired-end FASTQ files were processed using default parameters of Kallisto version v0.43.1, with 100 bootstraps for the expectation-maximization algorithm. Kallisto transcriptome index was built using the Ensembl human genome reference build 38. Gene level summarization of Kallisto abundance (TPM) was established using the R package Tximport v1.0.3 and R v3.3.1.