The rapid endocytic uptake of fetuin‐A by adherent tumor cells is mediated by Toll‐like receptor 4 (TLR4). Issue 12 (3rd November 2020)

• Record Type: Journal Article
• Authors: Thomas, Portia L.; Nangami, Gladys; Rana, Tanu; Evans, Adam; Williams, Stephen D.; Crowell, Dylan; Shanker, Anil; Sakwe, Amos M.; Ochieng, Josiah
• Is Part Of: FEBS open bio. Volume 10:Issue 12(2020)
• Page Start: 2722
• Page End: 2732
• Publication Date: 2020-11-03
• Subjects: adhesion -- endocytosis -- fetuin‐A -- LPS -- receptor -- TLR4; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.13008
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : Fetuin‐A is a serum glycoprotein synthesized and secreted into blood by the liver and whose main physiological function is the inhibition of ectopic calcification. However, a number of studies have demonstrated that it is a multifunctional protein. For example, endocytic uptake of fetuin‐A by tumor cells resulting in rapid cellular adhesion and spreading has been reported. The precise uptake mechanism, however, has been elusive. The present studies were done to determine whether Toll‐like receptor‐4 (TLR4), which has been previously shown to be a receptor for fetuin‐A and is commonly expressed in immune cells, could take part in the rapid uptake (< 3 min) of fetuin‐A by tumor cells. Rapid uptake of fetuin‐A was inhibited by the specific TLR4 inhibitor CLI‐095 and also attenuated in TLR4 knockdown prostate tumor cells. Inhibition of TLR4 by CLI‐095 also attenuated the rapid adhesion of tumor cells as well as invasion through a bed of Matrigel. The data suggest mechanisms by which TLR4 modulates the adhesion and growth of tumor cells. Abstract : The study demonstrates that TLR4 mediates the rapid uptake of fetuin‐A by tumor cells to promote rapid adhesion, spreading, growth, motility, and invasion in serum‐free medium. The specific TLR4 inhibitor, CLI‐095, inhibits rapid fetuin‐A uptake, and consequently, most tumor cells, particularly those that do not synthesize fetuin‐A, fail to adhere, spread, or grow in serum‐free medium.