Downregulated CCND3 Is a Key Event Driving Lung Adenocarcinoma Metastasis during Acquired Cisplatin Resistance.

ABSTRACT: Cyclin D3 (CCND3), a member of the cyclin D family, is known to promote cell cycle transition. In this study, we found that CCND3 was downregulated in cisplatin-resistant (cis-diamminedichloroplatinum, DDP) lung adenocarcinoma (LUAD) cells. The loss of CCND3 indeed impeded cell cycle transition. Unexpectedly, its downregulation significantly triggered cytoskeleton remodeling and chemoresistance and accelerated LUAD metastasis in vivo and in vitro. Moreover, the clinical samples showed a significant negative correlation between CCND3 expression and lymphatic metastasis, as well as the unfavorable survival prognosis of patients with LUAD. Mechanistically, CCND3 downregulation in DDP-resistant LUAD cells was attributable to the transcriptional suppression of PI3K/Akt/c-Ju

SUBMITTER: Su Y 

PROVIDER: S-EPMC11705650 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature