Bis-indole derived nuclear receptor 4A1 (NR4A1) antagonists inhibit TGFβ-induced invasion of embryonal rhabdomyosarcoma cells.

ABSTRACT: Transforming growth factor β (TGFβ) enhances invasion of breast and lung cancer cells through phosphorylation-dependent nuclear export of the nuclear receptor 4A1 (NR4A1, Nur77). This response is inhibited by the NR4A1 antagonist 1,1-bis(3'-indoly)-1-(p-hydroxyphenyl) methane (CDIM8) and we hypothesized that similar effects would be observed in Rhabdomyosarcoma (RMS) cells. Although some kinase inhibitors block TGFβ-induced invasion of embryonal RMS (ERMS) cells, the mechanism differs from breast and lung cancer cells since NR4A1 is extranuclear in ERMS cells. However, CDIM8 blocks basal and TGFβ-induced invasion of RD and SMS-CTR ERMS cell lines but not Rh30 alveolar RMS (ARMS) cells. Moreover, this response in ERMS cells was independent of SMAD7 degradation or activation of SMAD2/SMAD3.

SUBMITTER: Shrestha R 

PROVIDER: S-EPMC7471359 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature