DNAJC5 facilitates the proliferation and migration of lung adenocarcinoma cells by augmenting EGFR trafficking

ABSTRACT: Lung adenocarcinoma (LUAD) is a highly prevalent and lethal malignant tumor, with the aberrantly activated EGFR signaling pathway playing a crucial role in its development. However, resistance to tyrosine-kinase inhibitors (TKIs) targeting EGFR significantly limits the efficacy of LUAD clinical therapy. Therefore, it is imperative to identify novel therapeutic targets and elucidate the regulatory mechanisms of EGFR for improving LUAD treatment outcomes. In this study, we discovered that DNAJC5 functions as an oncogene in LUAD. We observed elevated protein levels of DNAJC5 in tissues from LUAD patients, which were strongly associated with poor prognosis among these individuals. Furthermore, overexpression of DNAJC5 promoted proliferation and migration of LUAD cells both in vitro and in vivo. Mechanistic investigations revealed that DNAJC5 interacts with the intracellular domain of EGFR and enhances its endocytosis and recycle, thereby augmenting EGFR activity and downstream signaling pathways. Additionally, we found that DNAJC5 binds to AP2A1 protein—a key player in EGFR endocytosis—and strengthens its interaction with EGFR. Knockdown experiments targeting AP2A1 attenuated the ability of DNAJC5 to promote proliferation and migration of LUAD cells. Collectively, our findings unveil a functional role for DNAJC5 in regulating EGFR trafficking and driving LUAD progression.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: hailong wang  

LAB HEAD: Hailong Wang

PROVIDER: PXD063682 | Pride | 2025-05-26

REPOSITORIES: Pride