title: Nicotinic acid inhibits glioma invasion by facilitating Snail1 degradation.
abstract: Malignant glioma is a formidable disease that commonly leads to death, mainly due to the invasion of tumor cells into neighboring tissues. Therefore, inhibition of tumor cell invasion may provide an effective therapy for malignant glioma. Here we report that nicotinic acid (NA), an essential vitamin, inhibits glioma cell invasion in vitro and in vivo. Treatment of the U251 glioma cells with NA in vitro results in reduced invasion, which is accompanied by a loss of mesenchymal phenotype and an increase in cell-cell adhesion. At the molecular level, transcription of the adherens junction protein E-cadherin is upregulated, leading to accumulation of E-cadherin protein at the cell-cell boundary. This can be attributed to NA's ability to facilitate the ubiquitination and degradation of Snail1, a transcription factor that represses E-cadherin expression. Similarly, NA transiently inhibits neural crest migration in Xenopus embryos in a Snail1-dependent manner, indicating that the mechanism of action for NA in cell migration is evolutionarily conserved. We further show that NA injection blocks the infiltration of tumor cells into the adjacent brain tissues and improves animal survival in a rat model of glioma. These results suggest that NA treatment may be developed into a potential therapy for malignant glioma.
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital of KMUST, Medical School, Kunming University of Science and Technology, Kunming 650032, China.|Department of Biology, West Virginia University, Morgantown, WV 26506, United States.
authors.forename: Jiejing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital of KMUST, Medical School, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Jiagui
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.|Ministry of Education Key Laboratory of Child Development and Disorders; Chongqing Key Laboratory of Pediatrics; Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Chongqing 400014, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Biology, West Virginia University, Morgantown, WV 26506, United States.|Department of Biological Sciences, University of Delaware, Newark, DE 19716, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Perfetto
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital of KMUST, Medical School, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Zhuxian
authors.initials: Z
authors.lastname: Ping
authors.affiliation: Department of Biology, West Virginia University, Morgantown, WV 26506, United States.
authors.forename: Laura
authors.initials: L
authors.lastname: Christian
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital of KMUST, Medical School, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Niu
authors.affiliation: Department of Gerontology, First People's Hospital of Yunnan Province, Kunming 650032, China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Mei
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital of KMUST, Medical School, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, The Affiliated Hospital of KMUST, Medical School, Kunming University of Science and Technology, Kunming 650032, China.
authors.forename: Xiangcai
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biology, West Virginia University, Morgantown, WV 26506, United States.|Department of Biological Sciences, University of Delaware, Newark, DE 19716, United States.
authors.forename: Shuo
authors.initials: S
authors.lastname: Wei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D004195:Disease Models, Animal; D005910:Glioma / Q000473:pathology*; D006801:Humans; D009525:Niacin / Q000008:administration & dosage / Q000378:metabolism*; D059748:Proteolysis; D051381:Rats; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D009525:Niacin