阿霉素
乳腺癌
癌症研究
PI3K/AKT/mTOR通路
MAPK/ERK通路
化疗
癌症
蛋白激酶B
医学
激酶
三阴性乳腺癌
内科学
肿瘤科
信号转导
生物
细胞生物学
作者
Zhiqiang Li,Miao Qu,Yang Sun,Hongxing Wan,Fang Chai,Lihong Liu,Peng Zhang
标识
DOI:10.1016/j.bbrc.2018.01.016
摘要
Advanced breast cancer is resistant to chemotherapy and its underlying mechanisms are not fully explored. In this work, we identified cytosolic phospholipase A2 alpha (cPLA2α) as a novel target to overcome chemoresistance in breast cancer. We demonstrated the increased transcriptional and translational expression of cPLA2α in breast cancer cells to acute and chronic exposure to doxorubicin. cPLA2α upregulation is also observed in breast cancer patients in response to chemotherapy. Inhibition of cPLA2α using two pharmacological inhibitors significantly enhances doxorubicin's effects to almost complete suppression in breast cancer cell growth, survival and migration. Similarly, depletion of cPLA2α significantly sensitizes breast cancer cells to doxorubicin treatment. We further found that cPLA2α inhibition led to decreased phosphorylation of ERK, mTOR, S6 and 4EBP1, suggesting the suppression of ERK and mTOR signaling pathways. These findings indicate the positive roles of cPLA2α in breast cancer cell growth, survival, migration and response to chemotherapy. Our work also highlights the therapeutic value of blocking cPLA2α to overcome chemoresistance in breast cancer.
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