title: Ulva pertusa lectin 1 delivery through adenovirus vector affects multiple signaling pathways in cancer cells.
abstract: Ulva pertusa lectin 1 (UPL1) is a N-acetyl-D-glucosamine (GlcNAc) binding lectin in marine green alga Ulva pertusa. Exogenous UPL1 colocalized with protein arginine methyltransferase 5 (PRMT5), methylosome protein 50 (MEP50), β-actin and β-tubulin, indicating the interaction of UPL1 with the methylosome and cytoskeleton. UPL1 delivery through adenovirus vector (Ad-UPL1) dramatically induced extracellularly regulated protein kinases 1/2 (ERK1/2) phosphorylation in liver cancer cell lines BEL-7404 and Huh7. Signaling pathways including p38 mitogen-activated protein kinase (MAPK), and Akt were also affected by Ad-UPL1 in a cell type dependent manner. MEK1/2 inhibitor U0126, as well as to a lesser extent p38 MAPK inhibitor SB203580 and phosphoinositide 3-kinase (PI3K) inhibitor LY294002, completely eliminated a higher molecular weight isoform of β-tubulin induced by Ad-UPL1, and significantly enhanced the cytotoxicity of Ad-UPL1 in Huh7 cells, suggesting that the inhibition of MEK1/2, p38 MAPK, and PI3K enhanced antiproliferative effect of Ad-UPL1 possibly through regulating the modification of β-tubulin. Ad-UPL1 completely inhibited the expression of autophagy-related factor Beclin1, but induced LC3-II expression in Huh7 cells. In addition, Ad-UPL1 significantly enhanced starvation induced survival suppression in Huh7 cells. Our data elucidated intracellular signaling pathways affected by exogenous UPL1, and may provide insights into a novel way of UPL1 delivery through adenovirus vectors combined with survival signaling inhibitors for cancer treatment.
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China. lgc@zstu.edu.cn.
authors.forename: Gongchu
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Wu
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Qunshu
authors.initials: Q
authors.lastname: Su
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Wu
authors.affiliation: College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Institute of Life Sciences, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005822:Genetic Vectors / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D037102:Lectins / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D044445:Ulva / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D037102:Lectins; D014404:Tubulin; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins
keywords: MEK1/2-ERK1/2; PI3K; Ulva pertusa lectin 1; p38 MAPK; β-tubulin