Frontiers in bioscience (Landmark edition) · 2026
COL11A1 Inhibits Ferroptosis in Pancreatic Cancer by Regulating AKT/Beclin 1 Dependent Autophagy.
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Wang Hui, Zhi Shuang, Yang Zibo, Gu Na, Dai Linlin, Cai Jun, Wang Juan, Li Dongdong
Аннотация
BACKGROUND: Collagen type XI alpha 1 (COL11A1) is overexpressed in pancreatic cancer and is often associated with poor survival, chemoresistance, and tumor recurrence. However, the role of COL11A1 in pancreatic cancer remains poorly understood.
METHODS: We explored the correlation between COL11A1 and overall survival in pancreatic cancer patients using Kaplan-Meier survival analysis and validated COL11A1's regulatory role in the viability of pancreatic cancer cell line PANC-1 using Cell Counting Kit-8 and colony formation assays. To clarify the underlying mechanisms, we further examined COL11A1's modulation of ferroptosis and autophagy in PANC-1 cells by western blot, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence assays. Moreover, autophagy agonist rapamycin, inhibitor 3-methyladenine (3-MA), and AKT/Beclin 1 pathway inhibitors were employed to dissect the regulatory crosstalk between COL11A1, autophagy, and ferroptosis.
RESULTS: COL11A1 expression was negatively correlated with pancreatic cancer patients' survival rate. Its overexpression significantly enhanced the viability and clonogenic capacity of erastin- and rapamycin-treated PANC-1 cells. Our data showed that COL11A1 reduced intracellular iron levels, suppressed reactive oxygen species accumulation, downregulated malondialdehyde and microtubule-associated protein 1 light chain 3-II/I (LC3II/I) expression, while increasing glutathione (GSH), ferritin heavy chain 1 (FTH1) and solute carrier family 7 member 11 (SLC7A11) levels. Furthermore, COL11A1-mediated ferroptosis inhibition was attenuated by the autophagy agonist Rapamycin but enhanced by the inhibitor 3-MA. Notably, COL11A1 promoted AKT and Beclin 1 phosphorylation, and blocking the AKT/Beclin 1 pathway abrogated its ability to suppress autophagy and ferroptosis in pancreatic cancer cells.
CONCLUSIONS: The study demonstrated that COL11A1 exerts its oncogenic effects by suppressing autophagy via the AKT/Beclin 1 pathway, consequently inhibiting ferroptosis in pancreatic cancer cells. These findings reveal a novel molecular mechanism through which COL11A1 promotes tumor progression and provide a potential therapeutic target for pancreatic cancer treatment.
METHODS: We explored the correlation between COL11A1 and overall survival in pancreatic cancer patients using Kaplan-Meier survival analysis and validated COL11A1's regulatory role in the viability of pancreatic cancer cell line PANC-1 using Cell Counting Kit-8 and colony formation assays. To clarify the underlying mechanisms, we further examined COL11A1's modulation of ferroptosis and autophagy in PANC-1 cells by western blot, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence assays. Moreover, autophagy agonist rapamycin, inhibitor 3-methyladenine (3-MA), and AKT/Beclin 1 pathway inhibitors were employed to dissect the regulatory crosstalk between COL11A1, autophagy, and ferroptosis.
RESULTS: COL11A1 expression was negatively correlated with pancreatic cancer patients' survival rate. Its overexpression significantly enhanced the viability and clonogenic capacity of erastin- and rapamycin-treated PANC-1 cells. Our data showed that COL11A1 reduced intracellular iron levels, suppressed reactive oxygen species accumulation, downregulated malondialdehyde and microtubule-associated protein 1 light chain 3-II/I (LC3II/I) expression, while increasing glutathione (GSH), ferritin heavy chain 1 (FTH1) and solute carrier family 7 member 11 (SLC7A11) levels. Furthermore, COL11A1-mediated ferroptosis inhibition was attenuated by the autophagy agonist Rapamycin but enhanced by the inhibitor 3-MA. Notably, COL11A1 promoted AKT and Beclin 1 phosphorylation, and blocking the AKT/Beclin 1 pathway abrogated its ability to suppress autophagy and ferroptosis in pancreatic cancer cells.
CONCLUSIONS: The study demonstrated that COL11A1 exerts its oncogenic effects by suppressing autophagy via the AKT/Beclin 1 pathway, consequently inhibiting ferroptosis in pancreatic cancer cells. These findings reveal a novel molecular mechanism through which COL11A1 promotes tumor progression and provide a potential therapeutic target for pancreatic cancer treatment.