Endogenous and exogenous galectin-3 promote the adhesion of tumor cells with low expression of MUC1 to HUVECs through upregulation of N-cadherin and CD44

Cao, Zhanqi, Hao, Zhaojun, Xin, Ming, Yu, Lugang ORCID: 0000-0001-9641-3712, Wang, Lei, Zhang, Ying, Zhang, Xinke and Guo, Xiuli (2018) Endogenous and exogenous galectin-3 promote the adhesion of tumor cells with low expression of MUC1 to HUVECs through upregulation of N-cadherin and CD44. Laboratory Investigation, 98 (12). pp. 1642-1656.

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Official URL: https://www.nature.com/articles/s41374-018-0119-3

Abstract

Tumor cell-endothelial adhesion is one of the key steps in tumor cell haematogenous dissemination in metastasis and was previously shown to be mediated by interaction of galectin-3 with the transmembrane mucin protein MUC1. In this study, the effect of exogenous as well as endogenous galectin-3 on adhesion of two cell lines (low MUC1-expressing human prostate cancer PC-3M cells and non-small-cell lung cancer A549 cells) to monolayer of umbilical vein endothelial cells (HUVECs) was investigated. We found that suppression of endogenous galectin-3 expression reduced tumor cell adhesion to HUVECs and also decreased cell invasion and migration. Exogenous galectin-3 promoted tumor cell adhesion to HUVECs by entering cells. Both exogenous and endogenous galectin-3 upregulated the expression of β-catenin and increased β-catenin nuclear accumulation, and subsequently upregulated the expression of N-cadherin and CD44. We deduced that both exogenous as well as endogenous galectin-3 promoted low MUC1-expressing cancer cell adhesion to HUVECs by increasing the expression of N-cadherin and CD44 via an increase of nuclear β-catenin accumulation. These results were confirmed further by using a β-catenin/TCF transcriptional activity inhibitor, N-cadherin or CD44 siRNAs. Taken together, our results suggest a new molecular mechanism of galectin-3-mediated cell adhesion in cancer metastasis.

Item Type:	Article
Uncontrolled Keywords:	Metastasis, Tumour biomarkers
Depositing User:	Symplectic Admin
Date Deposited:	14 Sep 2018 15:48
Last Modified:	19 Jan 2023 01:17
DOI:	10.1038/s41374-018-0119-3
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3026291