Upregulation of annexin A1 expression by butyrate in human melanoma cells induces invasion by inhibiting E-cadherin expression.
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.
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, 138-736, South Korea.|Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 138-736, South Korea.|Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, South Korea.
Jimin
J
Shin
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, 138-736, South Korea.|Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 138-736, South Korea.|Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, South Korea.
In-Sung
IS
Song
Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, South Korea.
Jhang Ho
JH
Pak
Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, 138-736, South Korea. swjang@amc.seoul.kr.|Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 138-736, South Korea. swjang@amc.seoul.kr.
Sung-Wuk
SW
Jang
D017305:Annexin A1 / Q000096:biosynthesis* / Q000235:genetics; D002087:Butyrates / Q000494:pharmacology*; D015820:Cadherins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D012878:Skin Neoplasms; D015854:Up-Regulation / Q000187:drug effects; D000096142:Cutaneous Malignant Melanoma
D017305:Annexin A1; D002087:Butyrates; D015820:Cadherins; D012333:RNA, Messenger; D034741:RNA, Small Interfering
EMT; Annexin A1; E-cadherin