TIPE2 sensitizes breast cancer cells to paclitaxel by suppressing drug-induced autophagy and cancer stem cell properties

Drug resistance is a great obstacle to the clinical application of paclitaxel (PTX) in breast Cancer treatment. Chemoresistance can be either primary or acquired. Multifarious factors are related to drug resistance. Among these factors, drug-induced Autophagy has been shown to contribute to acquired chemoresistance in Cancer cells. Additionally, Cancer Stem Cells (CSCs) drive primary chemoresistance. Recent advances regarding TIPE2 demonstrate that TIPE2 enhances osteosarcoma and non-small cell lung Cancer cell sensitivity to cisplatin. However, the role of TIPE2 in PTX resistance in breast Cancer cells has not been elucidated. Here, the in vitro and in vivo study demonstrated that TIPE2 sensitized breast Cancer cells to PTX by suppressing drug-induced Autophagy and CSC properties. Mechanistically, we found that TIPE2 activated the Akt/mTOR signalling pathway and inhibited the TAK1/MAPK signalling pathway to suppress drug-induced Autophagy. Moreover, TIPE2 inhibited TAK1/NF-κB activation to reduce breast CSC properties. Collectively, our results first elucidated the inhibitory role of TIPE2 in breast Cancer chemoresistance. Thus, TIPE2 may be a new target for breast Cancer chemotherapy.

Autophagy; Breast cancer; Cancer stem cells; Drug sensitivity; TIPE2.