Redox report : communications in free radical research · 2026
PRX5 as a critical driver of colorectal cancer stemness and tumorigenicity.
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Lee Sung Woo, Park Sun-Ji, Lee Ga Eun, Jung Su-Min, Lee Jaeyeon, Kwon San, Yeom Eunbyul, Lee Dong-Seok, Choi Eui-Hwan
Аннотация
BACKGROUND: Cancer stem cells (CSCs) support colorectal cancer progression and therapy resistance, yet the redox regulators that sustain CSC identity are incompletely defined. We investigated the role of peroxiredoxin 5 (PRX5) in CSC formation and tumorigenicity using HCT116 colorectal cancer models.
METHODS: CSCs were enriched by serum-free spheroid culture and characterized by qPCR and western blotting for pluripotency and surface markers. PRX5 expression was regulated via siRNA or shRNA gene disruption and overexpression. Intracellular ROS was measured with DCF-DA staining. STAT3 activation was analyzed by p-STAT3 immunoblot. Functional assays included sphere formation, extreme limiting dilution analysis (ELDA), colony formation, and in vivo xenograft tumorigenicity in BALB/c-nu mice.
RESULTS: Spheroid induction selectively upregulated PRX5 among PRX isoforms. Efficient PRX5 knockdown (>95%) reduced OCT4, SOX2, NANOG, and CD133 expression, increased intracellular ROS, lowered p-STAT3 levels, and decreased sphere-forming frequency. Conversely, PRX5 overexpression enhanced pluripotency marker expression and proliferation. In vivo, PRX5-overexpressing xenografts grew faster, achieving a 2.5-fold greater tumor volume by day 19 and a 1.82-fold higher mean tumor weight compared with controls. Tumor tissues showed elevated OCT4, SOX2, NANOG, CD133, and EPCAM.
CONCLUSION: PRX5 contributes to maintaining a redox environment associated with STAT3 activation and core stemness programs in CRC, promoting CSC phenotypes and tumorigenicity. Targeting PRX5-mediated redox signaling may warrant further investigation as a potential approach to disrupt CSC maintenance and overcome chemoresistance.
METHODS: CSCs were enriched by serum-free spheroid culture and characterized by qPCR and western blotting for pluripotency and surface markers. PRX5 expression was regulated via siRNA or shRNA gene disruption and overexpression. Intracellular ROS was measured with DCF-DA staining. STAT3 activation was analyzed by p-STAT3 immunoblot. Functional assays included sphere formation, extreme limiting dilution analysis (ELDA), colony formation, and in vivo xenograft tumorigenicity in BALB/c-nu mice.
RESULTS: Spheroid induction selectively upregulated PRX5 among PRX isoforms. Efficient PRX5 knockdown (>95%) reduced OCT4, SOX2, NANOG, and CD133 expression, increased intracellular ROS, lowered p-STAT3 levels, and decreased sphere-forming frequency. Conversely, PRX5 overexpression enhanced pluripotency marker expression and proliferation. In vivo, PRX5-overexpressing xenografts grew faster, achieving a 2.5-fold greater tumor volume by day 19 and a 1.82-fold higher mean tumor weight compared with controls. Tumor tissues showed elevated OCT4, SOX2, NANOG, CD133, and EPCAM.
CONCLUSION: PRX5 contributes to maintaining a redox environment associated with STAT3 activation and core stemness programs in CRC, promoting CSC phenotypes and tumorigenicity. Targeting PRX5-mediated redox signaling may warrant further investigation as a potential approach to disrupt CSC maintenance and overcome chemoresistance.