Hypophosphorylation of retinoic acid receptor alpha inhibits triple-negative breast cancer cell migration and invasion

Retinoic acid receptor ? (RAR?) is a transcription factor that plays an essential role in tumor progression. Triplenegative breast cancer (TNBC) subtype of carcinoma with poor prognosis due to early therapeutic escape from conventional treatments and aggressive metastatic relapse by the occurrence epithelial-mesenchymal transition (EMT). However, as expression level RAR? does not correlate overall survival TNBC patients, we speculate post-translational modification such phosphorylation may be involved EMT metastasis. After overexpressing phosphorylation-defective mutant at serine 77 residue (RAR?S77A), found hypophosphorylation inhibited MDA-MB-231 cell motility migration vitro while reducing lung potential vivo. This was accompanied increased epithelial marker E-cadherin decreased mesenchymal markers ?-catenin zinc finger E-box-binding homeobox 1 (ZEB1) agreement suppression EMT. Interestingly, overexpression wild-type presence agonist AM580 failed suppress migration. These results indicate hypophosphorylated RAR?S77 can directly mimic activated inhibit migration/invasion cells, thus providing novel target intervention TNBC.