<br/>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-<i>trans</i>-retinoic acid receptor (RAR) agonists on K562 cellular adhesion, proliferation, and α5β1 integrin cell surface expression was investigated.  RARgamma 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 RARgamma- 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 significant differences in K562 cell surface expression of the a5 integrin subunit when cells were exposed to RARα, RARβ, or RARgamma agonists for all time points tested.  In contrast, RARgamma agonist exposure resulted in a significant 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 RARgamma 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 RARgamma 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 erythromyeblastoid leukemia cell line.<br/>

Retinoic acid receptor gamma reciprocally regulates cellular adhesion and proliferation in K562 cells

253rd National Meeting (2017)

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