14, 15-EET induces breast cancer cell EMT and cisplatin resistance by up-regulating integrin αvβ3 and activating FAK/PI3K/AKT signaling

Luo, Jing; Yao, Jianfeng; Deng, Xiaofei; Zheng, Xiaodan; Jia, Min; Wang, Yueqin; Huang, Yan; Zhu, Jianhua

doi:10.1186/s13046-018-0694-6

Cited by 132 publications

(89 citation statements)

References 42 publications

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“…Luo et al identified FAK/PI3K/AKT activation in response to 14,15- EET, through the upregulation of avb3 integrin, with the responses attenuated by 14,15-EEZE, a 14,15-EET antagonist. Lastly, the investigators observed that in addition to promoting mesenchymal properties, 14,15-EET also protected breast cancer cells from cisplatin toxicity in vitro and in vivo using a mouse xenograft model (Luo et al, 2018). This is significant because it provides evidence of a novel role for 14,15-EET in cancer progression.…”

Section: Breast Cancermentioning

confidence: 93%

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Expression and Function of Eicosanoid-Producing Cytochrome P450 Enzymes in Solid Tumors

et al. 2020

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Oxylipins derived from the oxidation of polyunsaturated fatty acids (PUFAs) act as important paracrine and autocrine signaling molecules. A subclass of oxylipins, the eicosanoids, have a broad range of physiological outcomes in inflammation, the immune response, cardiovascular homeostasis, and cell growth regulation. Consequently, eicosanoids are implicated in the pathophysiology of various diseases, most notably cancer, where eicosanoid mediated signaling is involved in tumor development, progression, and angiogenesis. Cytochrome P450s (CYPs) are a superfamily of heme monooxygenases generally involved in the clearance of xenobiotics while a subset of isozymes oxidize PUFAs to eicosanoids. Several eicosanoid forming CYPs are overexpressed in tumors, elevating eicosanoid levels and suggesting a key function in tumorigenesis and progression of tumors in the lung, breast, prostate, and kidney. This review summarizes the current understanding of CYPs' involvement in solid tumor etiology and progression providing supporting public data for gene expression from The Cancer Genome Atlas.

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Section: Breast Cancermentioning

confidence: 93%

“…Another study examining the effect of 14,15-EET in breast cancer demonstrated that 14,15-EET mediates epithelialmesenchymal transition (EMT) in breast cancer cell lines (Luo et al, 2018). EMT of cells is indicative of their metastatic capability as cells become more migratory and invasive.…”

Section: Breast Cancermentioning

confidence: 99%

Expression and Function of Eicosanoid-Producing Cytochrome P450 Enzymes in Solid Tumors

et al. 2020

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“…Ezrin promotes breast cancer progression by modulating AKT signals N Li et al Since EMT is an important component in tumour metastasis and invasion, 23 we next investigate the effect of Ezrin on EMT in BC. Interestingly, we found that when Ezrin was silenced, the BC cells attained an epithelial morphology and lost their migratory capability, whereas Ezrin overexpressed cells acquired a dispersed, spindle-shaped morphology (Supplemental Fig.…”

Section: Ezrin Promotes Bc Metastasis Via Emt In Vitro and In Vivomentioning

confidence: 99%

Ezrin promotes breast cancer progression by modulating AKT signals

Kong

Lin

et al. 2019

Br J Cancer

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BACKGROUND: Ezrin, which is known as a cytoskeleton linker protein, is closely linked with the metastatic progression of cancer and is frequently abnormally expressed in aggressive cancer types. However, the possible involvement of Ezrin in metastasis and angiogenesis in breast cancer remains unclear. METHODS: Immunohistochemical analysis of Ezrin was performed on both BC samples (n = 117) and normal epithelium samples (n = 47). In vivo and in vitro assays were performed to validate the effect of Ezrin on AKT pathway-mediated BC progression. RESULTS: In this study, Ezrin was found to be upregulated in BC tissues, which was linked with aggressive tumour characteristics and poor prognosis. Moreover, we showed that Ezrin promotes BC proliferation, migration, invasion, and angiogenesis in vitro and in vivo. Mechanistic analysis showed that Ezrin interacted with AKT, and promoted its kinase activity, thereby regulating the AKT pathway in BC. CONCLUSIONS: In all, we propose a model for an Ezrin/AKT oncoprotein axis, which provides novel insight into how Ezrin contributes to BC progression.

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“…Elevated EET concentrations are associated with co-upregulation of CYP450 epoxygenases CYP2C19 and CYP2J2, FABP4 and FABP5, and adipocyte signaling-related proteins in TNBC tumors [25]. EETs are also important in epithelial-mesenchymal transition (EMT) and resistance via the STAT and AKT signaling pathways [26][27][28][29][30]. From these observations, we hypothesized that FABP4 and FABP5 have dynamic roles in EET-mediated TNBC signaling, particularly in the activation of pathways involved in stromal interaction and metastasis transformation.…”

Section: Introductionmentioning

confidence: 99%

Deregulating the CYP2C19/Epoxy-Eicosatrienoic Acid-Associated FABP4/FABP5 Signaling Network as a Therapeutic Approach for Metastatic Triple-Negative Breast Cancer

Apaya

Hsiao

Yang

et al. 2020

Cancers

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Recurrence and metastasis are the main causes of triple-negative breast cancer (TNBC) mortality. On the basis of our clinical cohorts and integrative omics analyses, we hypothesized that understanding the interplay between fatty acid binding protein (FABP) and epoxy-eicosatrienoic acid (EET) driven metastatic progression can uncover a new opportunity for TNBC intervention. In this study, the biological relevance of increased protein expression of CYP2C19, FABP4, and FABP5 in TNBC tumors and in the TNBC cell line (MDA-MB-231), as well as its highly metastatic lung seeking variant (LM6) were delineated from publicly available datasets, shRNA-mediated knockdown, EET supplementation, cancer and stromal cell co-cultures, and an orthotopic and resection xenograft tumor mouse model. We found that the high expression levels of CYP2C19 and FABP4 and FABP5 are critical in TNBC metastatic transformation and stromal cell interactions. Furthermore, EET-associated nuclear translocation of FABP4 and FABP5 and nuclear accumulation of SREBP-2 or PPAR-γ influence TNBC cell proliferation, migratory transformation, and distal metastasis priming. Most notably, we uncovered novel bioefficacy and modes of action of the anticancer drug doxorubicin and a phytogalactolipid, 1,2-di-O-α-linolenoyl-3-O-β-galactopyranosyl-sn-glycerol (dLGG), which effectively attenuated TNBC recurrence and lung metastasis through deregulating the FABP/EET dynamics and levels. This study, therefore, introduces a novel approach to combating TNBC by targeting the FABP/EET/CYP-associated metastatic signaling network.

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14, 15-EET induces breast cancer cell EMT and cisplatin resistance by up-regulating integrin αvβ3 and activating FAK/PI3K/AKT signaling

Cited by 132 publications

References 42 publications

Expression and Function of Eicosanoid-Producing Cytochrome P450 Enzymes in Solid Tumors

Expression and Function of Eicosanoid-Producing Cytochrome P450 Enzymes in Solid Tumors

Ezrin promotes breast cancer progression by modulating AKT signals

Deregulating the CYP2C19/Epoxy-Eicosatrienoic Acid-Associated FABP4/FABP5 Signaling Network as a Therapeutic Approach for Metastatic Triple-Negative Breast Cancer

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