CD44v6-mediated regulation of gastric cancer stem cells: a potential therapeutic target

Gastric cancer is the fourth most common cause of cancer-related deaths globally. Cancer stem cells (CSCs) play an essential role in tumor initiation, development, and chemoresistance. However, the molecular mechanisms that regulate CSC traits in gastric cancer, particularly the role of CD44v6 as a key CSC marker, remain poorly understood. Here, we demonstrate that CD44v6 is markedly upregulated in gastric cancer tissues and correlates with poor prognosis. Functional assays, including colony formation, wound healing, proliferation, and apoptosis assays, show that CD44v6 enhances CSC characteristics, such as self-renewal, proliferation, migration, and cisplatin chemoresistance. CD44v6 knockdown effectively suppresses these aggressive phenotypes. Mechanistically, CD44v6 regulates the expression of key CSC markers, including CD24, CD133, EpCAM, as well as stemness-related transcription factors Oct-4 and Nanog. Additionally, CD44v6 enhances cell proliferation and drug resistance in both in vitro and in vivo experiments. Collectively, our findings highlight the significant role of CD44v6 in regulating gastric CSC traits, suggesting it's a potential as a biomarker and therapeutic target for improving gastric cancer treatment outcomes, particularly in overcoming chemoresistance.