Abstract
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.
Highlights
CD44 is highly expressed in most cancer cells and its cross-linking pattern is closely related to tumor migration and invasion
CD44 cross‐linking in breast cancer Since there are few studies involving CD44 cross-linking abnormalities in breast cancers (BrCas), we selected four BrCas cell lines with different degrees of malignancy to explore the expression of CD44 and CD44 cross-linking
To show the CD44 cross-linked status on BrCas cells, we treated the cells with BS3, a membrane-impermeable compound that cross-link only nearby proteins located within the length of the spacer
Summary
CD44 is highly expressed in most cancer cells and its cross-linking pattern is closely related to tumor migration and invasion. The underlying molecular mechanism regarding CD44 cross-linking during cancer cell metastasis is poorly understood. Malignant tumor metastasis is usually the leading cause of death in cancer patients [1]. As one of the adhesion molecules related to tumor metastasis, CD44, a receptor of hyaluronan (HA), is becoming attractive for its role as a stem cell marker [5, 6]. The function of CD44 in cancers is not fully understood, data have proved that CD44 activities are usually triggered by binding with its ligands, especially HA. As HA is a non-sulfated glycosaminoglycan which usually binds with the multiple sites on the receptors that can cause CD44 linking together, we and
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