title: Capn4 promotes epithelial-mesenchymal transition in human melanoma cells through activation of the Wnt/β-catenin pathway.
abstract: Melanoma, as one of the most highly metastatic types of cancer, is resistant to current treatment methods, including popular targeted molecular therapy. Consequently, it is essential to develop a deeper understanding of the mechanisms involved in melanoma progression so that alternative treatments may be identified. To date, accumulating evidence supports the use of calpains, including calpain small subunit 1 (also known as Capn4 or CAPNS1), which affect cancer progression through many pathways, such as epithelial‑mesenchymal transition (EMT), the Wnt/β-catenin (β-catenin) and the nuclear factor κB (NF-κB) signaling pathways. The EMT pathway is well known as one of the most important events in tumor metastasis. The present study observed cross-talk among the EMT, β-catenin and NF-κB pathways. To identify the underlying mechanisms of Capn4 activity in melanoma cells, we determined Capn4 expression by gene chip and immunohistochemistral analyses in melanoma tissues and cells in vitro. The extent of apoptosis as determined by TUNEL assay, DAPI staining, and cleaved-caspase-3 assay was increased in human melanoma cells in which Capn4 expression had been knocked down when compared with untreated cells. Transwell assays and xenograft tumorigenicity studies were also performed to assess the effects of Capn4 on migration and invasion in vitro and tumor growth in vivo, respectively. The levels of β-catenin, vimentin, E-cadherin and N-cadherin were altered in human melanoma cells as determined by western blot analysis assay. Our study demonstrated that Capn4 is an underlying target for melanoma treatment.
authors.affiliation: Department of Radiology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Enwen
authors.initials: E
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Chongqing Cancer Hospital and Institute and Cancer Center, Chongqing 400030, P.R. China.
authors.forename: Donglin
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Ear-Nose-Throat, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Chongqing Cancer Hospital and Institute and Cancer Center, Chongqing 400030, P.R. China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Medical Oncology, Chongqing Cancer Hospital and Institute and Cancer Center, Chongqing 400030, P.R. China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Guan
authors.affiliation: Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing Cancer Hospital and Institute and Cancer Center, Chongqing 400030, P.R. China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing Cancer Hospital and Institute and Cancer Center, Chongqing 400030, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yi
authors.affiliation: Department of Radiology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Shaolin
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction; D014162:Transfection; D060449:Wnt Signaling Pathway; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D016328:NF-kappa B; D034741:RNA, Small Interfering; D051176:beta Catenin; D002154:Calpain; D053148:Caspase 3; C527669:CAPNS1 protein, human