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

Abstract

Background CD44 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. Methods The 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. Results High 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. Conclusions Our 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.

ANKHD1 contributes to the malignant phenotype of triple‐negative breast cancer cells

“…In the MDA-MB-231 cell line, but not the MCF-7 cell line, ANKHD1 silencing decreased cell migration (p < .05; Figure 3e). This result also highlighted the lower migratory capacity of MCF-7 compared to MDA-MB-231 cells, as previously reported (Hu et al, 2020).…”

High Moesin Expression Is a Predictor of Poor Prognosis of Breast Cancer: Evidence From a Systematic Review With Meta-Analysis

“…One recent study showed that via upregulation of p-moesin, CD44 cross-linking increases the malignancy of breast cancer. Moesin knockdown attenuated the promoting effect of CD44 cross-linking on tumor cell invasion and metastasis (55). Recently, Luo et al (56) proposed a novel mechanism of MSN contributing to tumor invasion and metastasis.…”

FBXW2 suppresses breast tumorigenesis by targeting AKT-Moesin-SKP2 axis

“…Moesin functions as a potential oncogene in breast cancer by promoting cancer initiation, progression, and metastasis [ 6 , 27 – 29 ]. Further, it was found that Moesin is highly expressed in hormone receptor positive as well as negative breast cancer patients and its high-level expression is closely associated with poor prognosis [ 30 – 32 ].…”

“…Further, it was reported that suppression of NF-κB can result in serious host toxicity with minimum effect on the tumor [ 38 ] and therefore p65 is not an established cancer marker to develop therapeutic drugs. On the other hand, irrespective of hormone expression status, Moesin is known to be involved in breast cancer progression and metastasis [ 6 , 27 – 29 , 39 – 43 ] and is highly expressed in breast cancer [ 28 – 30 , 39 , 44 – 46 ]. Therefore, limiting Moesin expression level in breast cancer could be beneficial for the management of cancer progression.…”