机构：[1]Department of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.河北医科大学第四医院[2]Department of Breast Surgery, Xingtai People's Hospital, Xingtai, Hebei, China.[3]Department of Pharmacology, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China.[4]Department of Radiotherapy, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.河北医科大学第四医院
Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic drugs. However, DOX resistance is a critical risk problem for breast cancer treatment. Previous studies have demonstrated that metadherin (MTDH) involves in DOX resistance in breast cancer, but the exact mechanism remains unclear. In this study, we found that glutaminyl-peptide cyclotransferase (QPCT) was a MTDH DOX resistance-related downstream gene in breast cancer. Elevated expression of QPCT was found in the GEPIA database, breast cancer tissue, and breast cancer cells. Clinical data showed that QPCT expression was positively associated with poor prognosis in DOX-treated patients. Overexpression of QPCT could promote the proliferation, invasion and migration, and reduce DOX sensitivity in MCF-7 and MDA-MB-231 cells. Mechanistically, MTDH positively regulates the expressions of NF-κB (p65) and QPCT, and NF-κB (p65) directly regulates the expression of QPCT. Therefore, MTDH/NF-κB (p65)/QPCT signal axis was proposed. Collectively, our findings delineate the mechanism by which the MTDH/NF-κB (p65) axis regulate QPCT signaling and suggest that this complex may play an essential role in breast cancer progression and affect DOX sensitivity.
基金：
This study is supported by the National Natural Science Foundation of China (NSFC, 81773828), Hebei Province Natural Science Foundation (H20202063, H2021206071) and the Wu Jieping Medical Foundation for Clinical Scientific Research (320.6750.2020-07-17, 320.6750.13295).
第一作者机构：[1]Department of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Breast Center, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
推荐引用方式(GB/T 7714)：
Xu Bin,Yang Liu,Yang Lixian,et al.Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity[J].CANCER BIOLOGY & THERAPY.2024,25(1):2321767.doi:10.1080/15384047.2024.2321767.
APA：
Xu Bin,Yang Liu,Yang Lixian,Al-Maamari Ahmed,Zhang Jingyu...&Song Zhenchuan.(2024).Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity.CANCER BIOLOGY & THERAPY,25,(1)
MLA：
Xu Bin,et al."Role of glutaminyl-peptide cyclotransferase in breast cancer doxorubicin sensitivity".CANCER BIOLOGY & THERAPY 25..1(2024):2321767
