@Article{or.2025.067628,
AUTHOR = {Fangyuan Li, Xiaoyuan Hu, Xiaoge Gao, Ling Liu, Tao Li, Dan He, Jiaxing Cheng, Xiaobiao Ma, Li Li, Chunlei Ge, Hong Yao},
TITLE = {PFDN6L Gene Predicts Good Prognosis Associated with Its Inhibition of the Stem-Ness Properties in Hepatocellular Carcinoma},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {12},
PAGES = {4029--4048},
URL = {http://www.techscience.com/or/v33n12/64628},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> Liver cancer stem cells (LCSCs) are recognized as pivotal drivers of hepatocellular carcinoma (HCC) progression; however, the molecular mechanisms maintaining their stem-like phenotype remain largely unresolved. This work investigates the role of prefoldin subunit 6-like protein (PFDN6L) in shaping LCSC traits and promoting or restraining HCC progression. <b>Methods:</b> PFDN6L, a cytoskeleton-associated chaperone, was studied using multiple <i>in vitro</i> assays—cell growth evaluation, cell cycle profiling, and spheroid culture—alongside analyses of stemness-associated markers (SOX2, CD133, CD44). Tumorigenic capacity was assessed in xenograft mouse models, and signaling pathway interrogation was performed to define underlying mechanisms. <b>Results:</b> In patient samples, higher PFDN6L expression correlated with improved survival outcomes. Forced expression of PFDN6L induced G2/M arrest, diminished sphere formation, and reduced pluripotency marker expression, whereas knockdown accelerated <i>in vivo</i> tumor formation. Mechanistic experiments demonstrated that PFDN6L suppresses malignancy by simultaneously dampening AKT and ERK1/2 activation, thereby impairing oncogenic signaling cascades. <b>Conclusion:</b> PFDN6L acts as a negative regulator of LCSC-driven tumorigenesis. Its dual blockade of AKT and ERK pathways forms the mechanistic basis of its tumor-suppressive action, supporting its potential as a prognostic biomarker and therapeutic target in HCC.},
DOI = {10.32604/or.2025.067628}
}