Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, T; McGoldrick, Liam J.; Bridges, Lance C.

doi:10.1016/j.bbrc.2014.10.120

Cited by 1 publication

(2 citation statements)

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“…All- trans -retinoic acid and 9- cis -retinoic acid have been implicated in modulating integrin-dependent and -independent cellular adhesion [18, 33, 35, 43]. Interestingly, we observe a slight but significant increase in cellular adhesion when cells were exposed to the RARα agonist for 96 hours on the fibronectin ligand (Fig 1B).…”

Section: Discussionmentioning

confidence: 71%

“…This study demonstrated that 9- cis -RA exposure did not increase α8, β3, αvβ5, or αvβ3 integrins on the cell surface of K562 cells and this data reflects very low surface levels regardless of vehicle or 9- cis -RA treatment group. Recently, the RARα specific isotype has been shown to induce integrin-independent cellular adhesion in RPMI 8866 cells [43]. It is plausible to suggest K562 cells exposed to the RARα agonist for 96 hours may have acquired integrin-independent adhesion strategies that are dependent on classical retinoid induced genetic modifications.…”

Section: Discussionmentioning

confidence: 99%

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Retinoic acid receptor gamma impacts cellular adhesion, Alpha5Beta1 integrin expression and proliferation in K562 cells

et al. 2017

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The interplay between cellular adhesion and proliferation is complex; however, integrins, particularly the α5β1 subset, play a pivotal role in orchestrating critical cellular signals that culminate in cellular adhesion and growth. Retinoids modify the expression of a variety of adhesive/proliferative signaling proteins including α5β1 integrins; however, the role of specific retinoic acid receptors involved in these processes has not been elucidated. In this study, the effect of all-trans-retinoic acid receptor (RAR) agonists on K562 cellular adhesion, proliferation, and α5β1 integrin cell surface expression was investigated. RARγ agonist exposure increased K562 cellular adhesion to RGD containing extracellular matrix proteins fibronectin and FN-120 in a time- and concentration dependent manner, while RARα or RARβ agonist treatment had no effect on cellular adhesion. Due to the novel RARγ- dependent cellular adhesion response exhibited by K562 cells, we examined α5 and β1 integrin subunit expression when K562 cells were exposed to retinoid agonists or vehicle for 24, 48, 72 or 96 hours. Our data demonstrates no differences in K562 cell surface expression of the α5 integrin subunit when cells were exposed to RARα, RARβ, or RARγ agonists for all time points tested. In contrast, RARγ agonist exposure resulted in an increase in cell surface β1 integrin subunit expression within 48 hours that was sustained at 72 and 96 hours. Finally, we demonstrate that while exposure to RARα or RARβ agonists have no effect on K562 cellular proliferation, the RARγ agonist significantly dampens K562 cellular proliferation levels in a time- and concentration- dependent manner. Our study is the first to report that treatment with a RARγ specific agonist augments cellular adhesion to α5β1 integrin substrates, increases cell surface levels of the β1 integrin subunit, and dampens cellular proliferation in a time and concentration dependent manner in a human erythroleukemia cell line.

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