Colorectal cancer(CRC)remains a major global health challenge,with high recurrence and mortality despite advances in surgery,chemotherapy,and immunotherapy.The study by He et al identifies a novel mechanism by which p...Colorectal cancer(CRC)remains a major global health challenge,with high recurrence and mortality despite advances in surgery,chemotherapy,and immunotherapy.The study by He et al identifies a novel mechanism by which peroxiredoxin 1(Prdx1)inhibits CRC progression through induction of pyroptosis,a pro-inflammatory form of programmed cell death.Traditionally viewed as an intracellular antioxidant that protects tumors from oxidative stress,Prdx1 assu-mes a paradoxical immunogenic role when released extracellularly as a damageassociated molecular pattern.Using patient samples,recombinant protein assays,and murine xenograft models,the authors demonstrate that Prdx1 activates the NOD-,LRR-and pyrin domain-containing protein 3 inflammasome/caspase-1/gasdermin D pathway,triggering membrane pore formation,tumor cell lysis,and release of interleukin-1β/interleukin-18.This cascade not only halts tumor proliferation,invasion,and migration but may also enhance anti-tumor immune surveillance.The study’s strengths include rigorous mechanistic validation,clinical cohort data,inhibitor-based causal proof,and in vivo confirmation.However,questions remain regarding the upstream receptor for Prdx1,heterogeneity across CRC subtypes,and the balance between therapeutic benefit and inflammatory toxicity.By establishing Prdx1-induced pyroptosis as a driver of tumor suppression,this work advances a promising paradigm in CRC therapy,linking cell death to immune activation and pointing toward future biomarker-driven,pyroptosis-based interventions.展开更多
BACKGROUND Damage associated molecular patterns(DAMPs)are vital for the immunogenic cell death of cancer cells and can enhance the anti-tumor activity of immune cells in colorectal cancer(CRC).Peroxiredoxin 1(Prdx1),a...BACKGROUND Damage associated molecular patterns(DAMPs)are vital for the immunogenic cell death of cancer cells and can enhance the anti-tumor activity of immune cells in colorectal cancer(CRC).Peroxiredoxin 1(Prdx1),an important DAMP,is highly expressed in various tumor tissues including CRC.However,the role of Prdx1 in CRC remains unknown.AIM To investigate the effect and mechanisms of Prdx1 on CRC.METHODS Patients diagnosed with CRC in our medical center were included in this study to verify the expression of Prdx1 in cancer tissues.Recombinant Prdx1(rPrdx1)was used to stimulate RKO and SW480 colon cancer cells.The cell survival rate,migration,proliferation and invasion ability were assessed.Transmission electron microscopy,TUNEL assay,lactate dehydrogenase release assay,and Western blot were used to determine the effect of Prdx1 on pyroptosis.NLRP3 inflammasome inhibitor and gasdermin D(GSDMD)inhibitor were used to explore the mechanism of Prdx1-induced pyroptosis.RESULTS The mRNA and protein levels of Prdx1 were significantly increased in the tumor tissues of patients with CRC.rPrdx1 inhibited the viability,proliferation,migration and invasion of RKO and SW480 colon cancer cells.Further study found that rPrdx1 inhibited the malignant biological behaviors of CRC cells by inducing pyroptosis rather than apoptosis and necroptosis.Mechanistically,rPrdx1 induces pyroptosis of CRC cells by activating the NLRP3 inflammasome/GSDMD pathway.CONCLUSION Prdx1 induces pyroptosis by activating the NLRP3 inflammasome/GSDMD pathway,thereby inhibiting the malignant biological behavior of RKO and SW480 colon cancer cells.展开更多
文摘Colorectal cancer(CRC)remains a major global health challenge,with high recurrence and mortality despite advances in surgery,chemotherapy,and immunotherapy.The study by He et al identifies a novel mechanism by which peroxiredoxin 1(Prdx1)inhibits CRC progression through induction of pyroptosis,a pro-inflammatory form of programmed cell death.Traditionally viewed as an intracellular antioxidant that protects tumors from oxidative stress,Prdx1 assu-mes a paradoxical immunogenic role when released extracellularly as a damageassociated molecular pattern.Using patient samples,recombinant protein assays,and murine xenograft models,the authors demonstrate that Prdx1 activates the NOD-,LRR-and pyrin domain-containing protein 3 inflammasome/caspase-1/gasdermin D pathway,triggering membrane pore formation,tumor cell lysis,and release of interleukin-1β/interleukin-18.This cascade not only halts tumor proliferation,invasion,and migration but may also enhance anti-tumor immune surveillance.The study’s strengths include rigorous mechanistic validation,clinical cohort data,inhibitor-based causal proof,and in vivo confirmation.However,questions remain regarding the upstream receptor for Prdx1,heterogeneity across CRC subtypes,and the balance between therapeutic benefit and inflammatory toxicity.By establishing Prdx1-induced pyroptosis as a driver of tumor suppression,this work advances a promising paradigm in CRC therapy,linking cell death to immune activation and pointing toward future biomarker-driven,pyroptosis-based interventions.
基金Supported by the National Natural Science Foundation of China,No.82302454Natural Science Foundation of Hunan Province,No.2025JJ60797,No.2025JJ60734 and No.2022JJ40718Guangdong Basic and Applied Basic Research Foundation,No.2022A1515111063.
文摘BACKGROUND Damage associated molecular patterns(DAMPs)are vital for the immunogenic cell death of cancer cells and can enhance the anti-tumor activity of immune cells in colorectal cancer(CRC).Peroxiredoxin 1(Prdx1),an important DAMP,is highly expressed in various tumor tissues including CRC.However,the role of Prdx1 in CRC remains unknown.AIM To investigate the effect and mechanisms of Prdx1 on CRC.METHODS Patients diagnosed with CRC in our medical center were included in this study to verify the expression of Prdx1 in cancer tissues.Recombinant Prdx1(rPrdx1)was used to stimulate RKO and SW480 colon cancer cells.The cell survival rate,migration,proliferation and invasion ability were assessed.Transmission electron microscopy,TUNEL assay,lactate dehydrogenase release assay,and Western blot were used to determine the effect of Prdx1 on pyroptosis.NLRP3 inflammasome inhibitor and gasdermin D(GSDMD)inhibitor were used to explore the mechanism of Prdx1-induced pyroptosis.RESULTS The mRNA and protein levels of Prdx1 were significantly increased in the tumor tissues of patients with CRC.rPrdx1 inhibited the viability,proliferation,migration and invasion of RKO and SW480 colon cancer cells.Further study found that rPrdx1 inhibited the malignant biological behaviors of CRC cells by inducing pyroptosis rather than apoptosis and necroptosis.Mechanistically,rPrdx1 induces pyroptosis of CRC cells by activating the NLRP3 inflammasome/GSDMD pathway.CONCLUSION Prdx1 induces pyroptosis by activating the NLRP3 inflammasome/GSDMD pathway,thereby inhibiting the malignant biological behavior of RKO and SW480 colon cancer cells.
