Upregulation of annexin A1 expression by butyrate in human melanoma cells induces invasion by inhibiting E-cadherin expression

Abstract

Epithelial to mesenchymal transition (EMT) is a critical step in the metastasis of epithelial cancer cells. Butyrate, which is produced from dietary fiber by colonic bacterial fermentation, has been reported to influence EMT. However, some studies have reported that butyrate promotes EMT, while others have reported an inhibitory effect. To clarify these controversial results, it is necessary to elucidate the mechanism by which butyrate can influence EMT. In this study, we examined the potential role of annexin A1 (ANXA1), which was previously reported to promote EMT in breast cancer cells, as a mediator of EMT regulation by butyrate. We found that ANXA1 mRNA and protein were expressed in highly invasive melanoma cell lines (A2058 and A375), but not in SK-MEL-5 cells, which are less invasive. We also showed that butyrate induced ANXA1 mRNA and protein expression and promoted EMT-related cell invasion in SK-MEL-5 cells. Downregulation of ANXA1 expression using specific small interfering RNAs in butyrate-treated SK-MEL-5 cells resulted in increased expression of the epithelial marker E-cadherin and decreased cell invasion. Moreover, overexpressing ANXA1 decreased the expression of the E-cadherin. Collectively, these results indicate that butyrate induces the expression of ANXA1 in human melanoma cells, which then promotes invasion through activating the EMT signaling pathway.

Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer

“…Since ANXA1 expression was linked to EMT in multiple cancer types [ 19 , 20 , 21 ], we first investigated the relationship between ANXA1 expression and EMT in PC. The EMT pathway activity was measured using the gene set variation analysis (GSVA) algorithm, following the method we previously reported [ 5 , 22 , 23 , 24 ].…”

DCST1-AS1 Promotes TGF-β-Induced Epithelial–Mesenchymal Transition and Enhances Chemoresistance in Triple-Negative Breast Cancer Cells via ANXA1

“…Alli-Shaik et al analyzed mammary epithelial cells from ANXA1-hybrid and ANXA1-deficient mice by quantitative phosphorylation proteomics and found that most ANXA1-responsive phosphorylation changes occurred in proteins involved in cytoskeletal reorganization, which favors (30). Overexpression of ANXA1 is often associated with EMT in some aggressive cancers (31,32). TGF-β/Smad signaling plays an important role in the progression of EMT in breast cancer, in which phosphorylation of Smad2 triggers the formation of a complex between Smad2 and Smad4, resulting in nuclear translocation of the Smad2/Smad4 complex and subsequent gene transcription (12,33,34).…”

Biomarkers of tumor invasiveness in proteomics (Review)

“…The keystone position of S100A4 in the acquisition of invasiveness by cancer cells can be illustrated by its inverse correlation with E-cadherin expression in different invasive phenotypes of oral squamous cell carcinoma (169). In melanoma cells, this inhibition of E-cadherin expression, which leads to EMT and increased invasiveness, has been shown to be associated with the upregulation of Annexin A1, which can be reversed by the use of small interfering RNAs (170). Overall, E-cadherin functional loss has been associated with a poor prognosis and survival in various types of cancer (171).…”