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...

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Published in:Human cell : official journal of Human Cell Research Society 2023-07, Vol.36 (4), p.1485-1500
Main Authors: Hu, Wei, Zheng, Wenxiang, Du, Jianxin, Tian, Zhaobing, Zhao, Yixin, Zhao, Peiqing, Li, Junsheng
Format: Article
Language:English
Subjects:
AKT protein
Autophagy
Biomedical and Life Sciences
Breast cancer
Cell Biology
Chemoresistance
Chemotherapy
Cisplatin
Drug resistance
Gynecology
Life Sciences
MAP kinase
NF-κB protein
Non-small cell lung carcinoma
Oncology
Osteosarcoma
Paclitaxel
Reproductive Medicine
Research Article
Signal transduction
Small cell lung carcinoma
Stem Cells
Surgery
TAK1 protein
TOR protein
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Summary: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.
ISSN:1749-0774
0914-7470
1749-0774
DOI:10.1007/s13577-023-00900-y