TY - EJOU
AU - Li, Fangyuan
AU - Hu, Xiaoyuan
AU - Gao, Xiaoge
AU - Liu, Ling
AU - Li, Tao
AU - He, Dan
AU - Cheng, Jiaxing
AU - Ma, Xiaobiao
AU - Li,
AU - Ge, Chunlei
AU - Yao, Hong
TI - PFDN6L Gene Predicts Good Prognosis Associated with Its Inhibition of the Stem-Ness Properties in Hepatocellular Carcinoma
T2 - Oncology Research
PY - 2025
VL - 33
IS - 12
SN - 1555-3906
AB - Background: 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. Methods: PFDN6L, a cytoskeleton-associated chaperone, was studied using multiple in vitro 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. Results: 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 in vivo tumor formation. Mechanistic experiments demonstrated that PFDN6L suppresses malignancy by simultaneously dampening AKT and ERK1/2 activation, thereby impairing oncogenic signaling cascades. Conclusion: 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.
KW - Hepatocellular carcinoma; liver cancer stem cells; prefoldin subunit 6-like protein (PFDN6L); prognosis
DO - 10.32604/or.2025.067628