title: Cullin3 promotes breast cancer cells metastasis and epithelial-mesenchymal transition by targeting BRMS1 for degradation.
abstract: Metastasis is the leading cause of death in breast cancer (BC) patients. However, until now, the mechanisms of BC metastasis remain elusive. Cullin3 is a highly conserved Cullin family member present in the genomes of all eukaryotes, which has been proposed as an oncogene in many types of tumors; however, its role and underlying mechanisms in BC remain unclear. Here we show that Cullin3 is elevated in BC and its expression level is positively correlated with metastasis. Overexpression of Cullin3 in BC cells increased proliferation, epithelial-mesenchymal transition, migration and invasion in vitro, and enhanced tumorigenic and metastatic capacities in vivo. In contrast, silencing Cullin3 in aggressive and invasive BC cells inhibited these processes. Mechanistically, we found Cullin3 exerts its function through promoting BRMS1 protein degradation, which was associated with EMT, migration and invasion. BRMS1 overexpression blocked Cullin3-driven EMT, and metastasis. Our results, for the first time, portray a pivotal role of Cullin3 in stimulating metastatic behaviors of BC cells. Targeting Cullin3 may thus be a useful strategy to impede BC cell invasion and metastasis.
authors.affiliation: Department of General Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Huo
authors.affiliation: Department of Oncology, Shaanxi Province Tumor Hospital, Xi'an, Shaanxi, 710061, China.
authors.forename: Suoni
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Shi
authors.affiliation: Department of Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors.forename: Aili
authors.initials: A
authors.lastname: Suo
authors.affiliation: Department of Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: Department of Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000328:Adult; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D044842:Cullin Proteins / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D059748:Proteolysis; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: C410024:BRMS1 protein, human; D044842:Cullin Proteins; D012097:Repressor Proteins
keywords: BRMS1; Cullin3; breast cancer; epithelial-mesenchymal transition; invasion