SIAH ubiquitin ligases regulate breast cancer cell migration and invasion independent of the oxygen status

Seven-in-absentia homolog (SIAH) proteins are evolutionary conserved RING type E3 ubiquitin ligasesresponsible for the degradation of key molecules regulating DNA damage response, hypoxic adaptation, apoptosis, angiogenesis, and cell proliferation. Many studies suggest a tumorigenic role for SIAH2. In breast cancer patients SIAH2expression levels correlate with cancer aggressiveness and overall patient survival. In addition, SIAH inhibition reduced metastasis in melanoma. The role of SIAH1in breast cancer is still ambiguous; both tumorigenic and tumor suppressive functions have been reported. Other studies categorized SIAH ligases as either pro- or antimigratory, while the significance for metastasis is largely unknown. Here, we re-evaluated the effects of SIAH1and SIAH2depletion in breast cancer cell lines, focusing on migration and invasion. We successfully knocked down SIAH1and SIAH2in several breast cancer cell lines. In luminal type MCF7 cells, this led to stabilization of the SIAH substrate P...