Role of SIPA1 in chemotherapy resistance in breast cancer cells

SIPA1 is a potential transcriptional modulator of tumor metastasis and recurrence. Here we showed that the breast cancer patients with higher SIPA1 expression have a higher relapse rate and worse prognosis, especially for triple-negative breast cancer (TNBC) patients. Moreover, SIPA1 expression was found positively correlated with relapse of breast cancer patients receiving adjuvant chemotherapy. In a TNBC cell line MDA-MB-231, we identified the possible tumorigenesis and metastasis processes regulated by SIPA1, and demonstrated that SIPA1 promoted cancer stem-like feature to form tumourspheres. Tumoursphere-formed MDA-MB-231 cells were shown to be resistant to epirubicin. Then we confirmed that SIPA1 could particularly activate the CD44 promoter and upregulate CD44 expression. Furthermore, SIPA1 could promote ABCB1 expression and strengthen chemoresistance of MDA-MB-231 cells to epirubicin. In conclusion, SIPA1 is a risk factor for highly-relapse in TNBC patients and a transcriptional regulator to maintain cancer stem-like features and promote chemoresistance in breast cancer cells. Overall design: Detection of DNA sequences bound to SIPA1 by ChIP-Seq in MDA-MB-231 cells.