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Glycoconj J. 2017 Aug;34(4):489-498. doi: 10.1007/s10719-017-9767-6. Epub 2017 Mar 27.

Ulva pertusa lectin 1 delivery through adenovirus vector affects multiple signaling pathways in cancer cells.

Author information

1
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China. lgc@zstu.edu.cn.
2
College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China.
3
Institute of Life Sciences, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China.

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.

KEYWORDS:

MEK1/2-ERK1/2; PI3K; Ulva pertusa lectin 1; p38 MAPK; β-tubulin

PMID:
28349379
DOI:
10.1007/s10719-017-9767-6
[Indexed for MEDLINE]

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