Trefoil Factor 1 contributes to Paclitaxel and Lapatinib resistance in brain metastatic breast cancer cells

Late occurrence of breast cancer brain metastases in patients pretreated with systemic therapies is often associated with therapy resistant brain metastatic lesions. Prior studies targeting previously identified mediators of resistance have yielded limited success, especially in the case of brain metastatic breast cancer (BMBC). Trefoil Factor 1 (TFF1) has been associated with therapy resistance in estrogen receptor (ER) positive breast cancer. However, its role in therapy resistance of triple negative and HER2+ breast cancer remains elusive. Herein, we assessed the involvement of TFF1 in therapy resistant triple negative and HER2+ BMBC. We developed Paclitaxel resistant triple negative and Lapatinib resistant HER2+ BMBC cells by dose escalation method. Drug efflux transporter ABCB1 in Paclitaxel resistant cells and ABCG2 in Lapatinib resistant cells were significantly upregulated. Additionally, cancer stem cell marker, CD24, showed significant upregulation in both resistant cell lines while anti-apoptotic protein BCL2 was upregulated only in Lapatinib resistant cells. Importantly, TFF1 was significantly upregulated in both Paclitaxel and Lapatinib resistant BMBC cells. Moreover, siRNA mediated TFF1 silencing partially alleviated resistance in both Paclitaxel and Lapatinib resistant BMBC cells. Our study shows that TFF1 is potentially associated with resistance to Paclitaxel and Lapatinib in both triple negative and HER2+ BMBC.