CD44 cross-linking increases malignancy of breast cancer via upregulation of p-Moesin.

CD44 cross-linking increases malignancy of breast cancer via upregulation of p-Moesin.
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CD44 交联通过上调 p-Moesin 增加乳腺癌的恶性程度

DOI:
10.1186/s12935-020-01663-4
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发表时间:
2020-11-23
影响因子:
5.8
通讯作者:
Gao F
Gao F
中科院分区:
医学2区
文献类型:
--
作者:
Hu S;Shi X;Liu Y;He Y;Du Y;Zhang G;Yang C;Gao F

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研究背景CD 44在大多数肿瘤细胞中高表达,其交联模式与肿瘤的迁移和侵袭密切相关。然而,在癌细胞转移过程中关于CD 44交联的潜在分子机制知之甚少。因此,本研究的目的是探讨是否破坏CD 44交联在乳腺癌细胞中可以阻止细胞的迁移和侵袭,并确定CD 44交联对癌细胞的恶性程度的影响。方法CD 44,CD 44交联和Moesin磷酸化在乳腺癌细胞中的表达通过Western Blot检测。Transwell法检测CD 44交联对肿瘤转移的影响。使用CCK-8测定评估CD 44交联破坏对细胞活力的影响。结果CD 44交联蛋白在浸润性乳腺癌细胞(BT-549和MDA-MB-231)中高表达,与乳腺癌的恶性程度有关。一组乳腺癌细胞系中ERM复合物的表达表明Moesin及其磷酸化可能在细胞转移中起重要作用。Moesin磷酸化被乳腺癌细胞中的CD 44去交联抑制,Moesin shRNA敲低减弱了CD 44交联对细胞迁移和侵袭的促进作用。最后,免疫组化结果表明,p-Moesin过表达在原发性和转移cancers.ConclusionsOur研究表明,CD 44交联可以提高p-Moesin的表达,并进一步影响迁移和乳腺癌细胞的侵袭。这些结果也表明,p-Moesin可能在未来的靶向癌症治疗中是有用的。
BackgroundCD44 is highly expressed in most cancer cells and its cross-linking pattern is closely related to tumor migration and invasion. However, the underlying molecular mechanism regarding CD44 cross-linking during cancer cell metastasis is poorly understood. Therefore, the purpose of this study was to explore whether disruption of CD44 cross-linking in breast cancer cells could prevent the cells migration and invasion and determine the effects of CD44 cross-linking on the malignancy of the cancer cells.MethodsThe expression of CD44, CD44 cross-linking and Moesin phosphorylation in breast cancer cells was assessed by Western Blot assays. Effects of CD44 cross-linking on tumor metastasis were evaluated by Transwell assay. The effects of CD44 cross-linking disruption on cell viability were assessed using CCK-8 assays. The expression of p-Moesin between normal and breast cancer tissues was examined by immunohistochemical staining.ResultsHigh expression of CD44 cross-linking was found in invasive breast cancer cells (BT-549 and MDA-MB-231), which is associated with the malignancy of breast cancer. The expressions of ERM complex in a panel of breast cancer cell lines indicate that Moesin and its phosphorylation may play a significant role in cell metastasis. Moesin phosphorylation was inhibited by CD44 de-crosslinking in breast cancer cells and Moesin shRNA knockdown attenuated the promotion of CD44 cross-linking on cell migration and invasion. Finally, immunohistochemistry results demonstrated that p-Moesin was overexpressed in primary and metastatic cancers.ConclusionsOur study suggested that CD44 cross-linking could elevate p-Moesin expression and further affect migration and invasion of breast cancer cells. These results also indicate that p-Moesin may be useful in future targeted cancer therapy.
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