Inhibition of TGFBIp expression reduces lymphangiogenesis and tumor metastasis

Oncogene
Y-S MaengEung Kweon Kim

Abstract

Transforming growth factor-β-induced protein (TGFBIp) is an extracellular matrix protein that has a role in a wide range of pathological conditions. However, the role of TGFBIp signaling in lymphangiogenesis is poorly understood. The purpose of this study was therefore to analyze the effects of TGFBIp on lymphangiogenesis and determine whether TGFBIp-related lymphangiogenesis is important for the metastasis of tumor cells. TGFBIp increased adhesion, migration, and morphologic differentiation of human lymphatic endothelial cells (LECs), consistent with an increase in lymphatic vessel sprouting in a three-dimensional lymphatic ring assay. TGFBIp also induced phosphorylation of intracellular signaling molecules SRC, FAK, AKT, JNK and ERK. TGFBIp-induced lymphatic vessel sprouting was inhibited by addition of anti-integrin β3 antibody and pharmacologic inhibitors of FAK, AKT, JNK or ERK. TGFBIp increased both CCL21 expression in LECs, a chemokine that actively recruits tumor cells expressing the cognate chemokine receptors to lymphatic vessels and LEC permeability by inducing the dissociation of VE-cadherin junctions between LECs via the activation of SRC signaling. In vivo, inhibition of TGFBIp expression in SW620 cancer cells dra...Continue Reading

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Citations

Dec 31, 2016·International Journal of Molecular Sciences·Rui-Cheng Ji
Jan 26, 2017·Yonsei Medical Journal·Yong Sun MaengEung Kweon Kim
Mar 13, 2017·Journal of Neuroimmunology·Thien NguyenIsaac Yang
Aug 29, 2019·Journal of Cellular and Molecular Medicine·Tong LinLan Gong
May 4, 2021·Cellular Signalling·Armando Corona, Gerard C Blobe

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