Scavenger receptor class B member 1 promotes lung cancer growth and metastasis through enhanced twist family BHLH transcription factor 1 signaling in vitro and in vivo: Exploration of RPPNs as a therapeutic Strategy.

OBJECTIVE: Lung cancer remains a leading cause of cancer-related mortality worldwide. Although scavenger receptor class B member 1 (SCARB1), a crucial cell surface receptor, plays a vital role in various cancers, its function in lung cancer remains incompletely elucidated. This study aims to investigate the role and molecular mechanisms of SCARB1 in lung cancer progression and develop a novel SCARB1-targeted nanoparticle drug delivery system. MATERIAL AND METHODS: We analyzed SCARB1 expression levels in lung cancer tissues and their correlation with patient prognosis using the Cancer Genome Atlas database. In vitro experiments, including quantitative real-time polymerase chain reaction, Western blot, 5-ethynyl-2'-deoxyuridine, colony formation, and Transwell analyses, were conducted to study the effects of SCARB1 on lung cancer cell proliferation, invasion, and migration. A lung metastasis model was established through tail vein injection to evaluate the role of SCARB1 in promoting lung cancer metastasis in vivo. We also developed red blood cell membrane-coated poly (lactic-co-glycolic acid) nanocarriers loaded with paclitaxel (RPPNs) and assessed their effect on SCARB1 expression and lung cancer progression. RESULTS: SCARB1 was overexpressed in human lung cancer tissues and significantly associated with poor patient prognosis. In vitro experiments confirmed that silencing SCARB1 inhibited lung cancer cell growth, invasion, and migration. SCARB1 overexpression promoted lung cancer cell proliferation, migration, and epithelial-mesenchymal transition through twist family BHLH transcription factor 1 (Twist1) activation. In vivo experiments further validated the crucial role of SCARB1 in promoting lung cancer metastasis. The developed RPPNs effectively suppressed SCARB1 expression in lung cancer and demonstrated superior inhibitory effects compared with traditional RPPNs. However, SCARB1 overexpression partially antagonized the antimetastatic effects of RPPNs. CONCLUSION: This work elucidates, for the 1(st) time, the molecular mechanism by which SCARB1 promotes lung cancer growth and metastasis through the activation of the Twist1 signaling pathway and develops a novel SCARB1-targeted nanoparticle drug delivery system, namely RPPNs. The findings of this work not only deepen our understanding of the molecular mechanisms underlying lung cancer progression but also provide new strategies for lung cancer diagnosis and treatment.