期刊
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
卷 37, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s13046-018-0694-6
关键词
Breast cancer; 14; 15-EET; EMT; Cisplatin resistance; alpha v beta 3/FAK/PI3K/AKT signaling
类别
资金
- National Natural Science Foundation of China [81502222]
- Natural Science Foundation of Hubei province [2013CFB370]
- China Postdoctoral Science Foundation [2016 M602311]
Background: 14,15-epoxyeicosatrienoic acid (14,15-EET) is an important lipid signaling molecule involved in the regulation of tumor metastasis, however, the role and molecular mechanisms of 14,15-EET activity in breast cancer cell epithelial-mesenchymal transition (EMT) and drug resistance remain enigmatic. Methods: The 14, 15-EET level in serum and in tumor or non-cancerous tissue from breast cancer patients was measured by ELISA. qRT-PCR and western blot analyses were used to examine expression of integrin alpha v beta 3. The role of 14, 15-EET in breast cancer cell adhesion, invasion was explored by adhesion and Transwell assays. The role of 14, 15-EET in breast cancer cell cisplatin resistance in vitro was determined by MTT assay. Western blot was conducted to detect the protein expressions of EMT-related markers and FAK/PI3K/AKT signaling. Xenograft models in nude mice were established to explore the roles of 14, 15-EET in breast cancer cells EMT and cisplatin resistance in vivo. Results: In the present study, we show that serum level of 14, 15-EET increases in breast cancer patients and 14, 15-EET level of tumor tissue is higher than that of non-cancerous tissue. Moreover, 14, 15-EET increases integrin alpha v beta 3 expression, leading to FAK activation. 14, 15-EET induces breast cancer cell EMT via integrin alpha v beta 3 and FAK/PI3K/AKT cascade activation in vitro. Furthermore, we find that 14, 15-EET induces breast cancer cells EMT and cisplatin resistance in vivo, alpha v beta 3 integrin and the resulting FAK/PI3K/AKT signaling pathway are responsible for 14, 15-EET induced-breast cancer cells cisplatin resistance. Conclusions: Our findings suggest that inhibition of 14, 15-EET or inactivation of integrin alpha v beta 3/FAK/PI3K/AKT pathway could serve as a novel approach to reverse EMT and cisplatin resistance in breast cancer cells.
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