Involvement of the ERK/HIF-1α/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells.
Involvement of the ERK/HIF-1α/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells.
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DOI：
10.3390/ijms22010089
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发表时间：
2020-12-23
影响因子：
5.6
通讯作者：
Cho J
中科院分区：
文献类型：
--
作者：
Do HTT;Cho J
趋化因子-受体相互作用在癌症进展中发挥多种作用。据报道，趋化因子X-C基序趋化因子配体1（XCL1）的特异性受体X-C基序趋化因子受体1（XCR1）的过度表达可刺激MDA-MB-231三阴性乳腺癌细胞的迁移。然而，这一过程的确切机制仍有待阐明。我们的研究发现 XCL1 处理显着增强 MDA-MB-231 细胞迁移。此外，XCL1 处理通过 E-钙粘蛋白下调和 N-钙粘蛋白和波形蛋白上调以及 β-连环蛋白核易位增加，增强了 MDA-MB-231 细胞的上皮-间质转化 (EMT)。此外，XCL1 增强缺氧诱导因子 1α (HIF-1α) 的表达和细胞外信号调节激酶 (ERK) 1/2 的磷酸化。值得注意的是，使用 siRNA 敲低 XCR1 可以消除 XCL1 对细胞迁移和细胞内信号转导的影响，从而证实了 XCR1 介导的作用。用 U0126（一种特异性丝裂原激活蛋白激酶激酶 (MEK) 1/2 抑制剂）处理 MDA-MB-231 细胞，可阻断 XCL1 诱导的 HIF-1α 积累和细胞迁移。还在 ER-/HER2+ SK-BR-3 细胞中评估了 XCL1 对细胞迁移的影响。 XCL1 还促进 SK-BR-3 细胞中的细胞迁移、EMT 诱导、HIF-1α 积累和 ERK 磷酸化。虽然 XCL1 对 MDA-MB-231 细胞中基质金属蛋白酶 (MMP)-2 和 -9 的表达没有表现出任何显着影响，但它增加了 SK-BR-3 细胞中这些酶的表达。总的来说，我们的结果表明 ERK/HIF-1α/EMT 通路的激活参与 XCL1 诱导的 MDA-MB-231 和 SK-BR-3 乳腺癌细胞的迁移。根据我们的研究结果，XCL1-XCR1 相互作用及其相关信号分子可能作为预防乳腺癌细胞迁移和转移的特定靶点。
Chemokine–receptor interactions play multiple roles in cancer progression. It was reported that the overexpression of X-C motif chemokine receptor 1 (XCR1), a specific receptor for chemokine X-C motif chemokine ligand 1 (XCL1), stimulates the migration of MDA-MB-231 triple-negative breast cancer cells. However, the exact mechanisms of this process remain to be elucidated. Our study found that XCL1 treatment markedly enhanced MDA-MB-231 cell migration. Additionally, XCL1 treatment enhanced epithelial–mesenchymal transition (EMT) of MDA-MB-231 cells via E-cadherin downregulation and upregulation of N-cadherin and vimentin as well as increases in β-catenin nucleus translocation. Furthermore, XCL1 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Notably, the effects of XCL1 on cell migration and intracellular signaling were negated by knockdown of XCR1 using siRNA, confirming XCR1-mediated actions. Treating MDA-MB-231 cells with U0126, a specific mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, blocked XCL1-induced HIF-1α accumulation and cell migration. The effect of XCL1 on cell migration was also evaluated in ER-/HER2+ SK-BR-3 cells. XCL1 also promoted cell migration, EMT induction, HIF-1α accumulation, and ERK phosphorylation in SK-BR-3 cells. While XCL1 did not exhibit any significant impact on the matrix metalloproteinase (MMP)-2 and -9 expressions in MDA-MB-231 cells, it increased the expression of these enzymes in SK-BR-3 cells. Collectively, our results demonstrate that activation of the ERK/HIF-1α/EMT pathway is involved in the XCL1-induced migration of both MDA-MB-231 and SK-BR-3 breast cancer cells. Based on our findings, the XCL1–XCR1 interaction and its associated signaling molecules may serve as specific targets for the prevention of breast cancer cell migration and metastasis.
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影响因子：
3.5
作者：
Homero Gutierrez-Aguirre, Cesar;Antonio Flores-Jimenez, Juan;Gomez-Almaguer, David
通讯作者：
Gomez-Almaguer, David
DOI：
10.1039/c9an01358j
发表时间：
2019-12-02
期刊：
The Analyst
影响因子：
--
作者：
Chen YC ;Sahoo S ;Brien R ;Jung S ;Humphries B ;Lee W ;Cheng YH ;Zhang Z ;Luker KE ;Wicha MS ;Luker GD ;Yoon E
通讯作者：
Yoon E
影响因子：
2.3
作者：
Hatzidaki, Eleana;Parsonidis, Panagiotis;Papasotiriou, Ioannis
通讯作者：
Papasotiriou, Ioannis
影响因子：
4.8
作者：
Gonzalez-Moles, M. A.;Ruiz-Avila, I.;Scully, C.
通讯作者：
Scully, C.
影响因子：
4.4
作者：
Cairns, CM;Gordon, JR;Xiang, J
通讯作者：
Xiang, J