To the best of our knowledge, this is the first report on β-catenin/TCF4-mediated p68 gene regulation, which plays an important role in epithelial to mesenchymal transition, as shown in vitro in breast cancer cell lines and in vivo in an animal breast tumour model.
Given the high frequency of DDX5 amplification in breast cancer, our results highlight DDX5 as a promising candidate for targeted therapy of breast tumors with DDX5 amplification, and indeed we show that DDX5 inhibition sensitizes a subset of breast cancer cells to trastuzumab.
Bioinformatical analysis revealed that the SUMO pathway is upregulated in breast tumors and that both p68 and p72 contain one consensus sumoylation site, implicating that sumoylation of p68 and p72 increases during breast tumorigenesis and potentially contributes to their overexpression.
Acetylation additionally increased the stability of p68 and p72 RNA helicase and stimulated their ability to coactivate the estrogen receptor, thereby potentially contributing to its aberrant activation in breast tumors.