The critical role of peroxiredoxin-2 in colon cancer stem cells

Abstract

Colon cancer stem cells (CCSCs) play an important role in facilitating colon cancer occurrence, metastasis and drug resistance. The results of our previous studies confirmed that the well-studied antioxidant gene peroxiredoxin-2 (PRDX2) promotes colon cancer progression. However, the underlying function and mechanisms associated with PRDX2 remodeling in the context of CCSCs have remained poorly studied. In our present study, we demonstrated that PRDX2 is highly expressed in CD133/CD44-positive colon cancer tissues and spheroid CD133+CD44+ CCSCs. PRDX2 overexpression was shown to be closely correlated with CD133+CD44+ CCSCs in colon cancer. Furthermore, PRDX2 depletion markedly suppressed CD133+CD44+ CCSC stemness maintenance, tumor initiation, migration and invasion and liver metastasis. Furthermore, the expression of various EMT markers and Wnt/β-catenin signaling proteins was altered after PRDX2 inhibition. In addition, PRDX2 knockdown led to increased ROS production in CD133+CD44+ CCSCs, sensitizing CCSCs to oxidative stress and chemotherapy. These results suggest that PRDX2 could be a possible therapeutic target in CCSCs.

Pharmacological inhibition of HDAC6 overcomes cisplatin chemoresistance by targeting cancer stem cells in oral squamous cell carcinoma

“…Previous studies demonstrated that CSC of OSCC show resistance to cisplatin through reduced oxidative stress, 18 and stem cells from pancreatic cancer exhibit high levels of PRDX2 19 . Also, PRDX2 knockdown inhibits tumor cell dedifferentiation in colorectal cancer, suggesting its importance to stemness maintenance 20 …”

“…19 Also, PRDX2 knockdown inhibits tumor cell dedifferentiation in colorectal cancer, suggesting its importance to stemness maintenance. 20 It is well reported that CSC can repair DNA damage. 21 By assessing the accumulation of phospho-H2A.X, we identified that the CSC present lower DNA damage than the non-stem cells subpopulation derived from cisplatin-resistant OSCC.…”

Redox-Regulation in Cancer Stem Cells

“…The authors conclude that the CD133/NRF2 axis contributes to the development of a CSC-like phenotype [ 105 ]. High expression of the antioxidant gene peroxiredoxin-2 ( PRDX2 ) has been attributed to CD133 + CD44 + cells and is associated with colon cancer CSC stemness [ 106 ]. Depletion of PRDX2 substantially suppressed maintenance of stemness, together with migration, invasion, and metastasis.…”

“…Depletion of PRDX2 substantially suppressed maintenance of stemness, together with migration, invasion, and metastasis. Notably, knockdown of PRDX2 increased ROS-levels in CD133 + CD44 + , making CSCs sensitive to oxidative stress and chemotherapy [ 106 ].…”

Papel da HDAC6 na regulação do estresse oxidativo e quimiorresistência de células-tronco tumorais em carcinoma oral

“…O estresse oxidativo promovido pelo acúmulo de espécies reativas de oxigênio (EROS) é um dos mecanismos de resposta ao câncer, que por sua vez ocasiona danos na molécula de DNA das células (LEE et al, 2020) KAMEMURA et al, 2012;PARMIGIANI et al, 2008b;RYU et al, 2017;TANG et al, 2018) PENG et al, 2021;WANG et al, 2016).…”