Redox regulation by SOD2 modulates colorectal cancer tumorigenesis through AMPK‐mediated energy metabolism

Abstract

Colorectal cancer (CRC) is a common malignancy. Many reports have implicated aberrant mitochondrial activity in the progression of CRC, with particular emphasis on the dysregulation of redox signaling and oxidative stress. In this study, we focused on manganese superoxide dismutase (MnSOD/SOD2), a key antioxidant enzyme, which maintains intracellular redox homeostasis. Current literature presents conflicting mechanisms for how SOD2 influences tumorigenesis and tumor progression. Here, we explored the role of SOD2 in CRC specifically. We found high levels of SOD2 expression in CRC tissues. We carried out a series of experiments to determine whether knockdown of SOD2 expression in CRC cell lines would reverse features of tumorigenesis. We found that reduced SOD2 expression decreased cell proliferation, migration, and invasion activity in CRC cells. Results from an additional series of experiments on mitochondrial function implicated a dual role for SOD2 in promoting CRC progression. First, proper level of SOD2 helped CRC cells maintain mitochondrial function by disposal of superoxide (O2.−). Second, over‐expression of SOD2 induced H2O2‐mediated tumorigenesis by upregulating AMPK and glycolysis. Our results indicate that SOD2 may promote the occurrence and development of CRC by regulating the energy metabolism mediated by AMPK signaling pathways.

Androgen-Dependent Prostate Cancer Cells Reprogram Their Metabolic Signature upon GLUT1 Upregulation by Manganese Superoxide Dismutase

“…These results might contrast with those from Zhou [ 25 ], where downregulation of SOD2 was associated with an increase in glucose uptake in colon cancer cells. In this case, the metabolism of the prostate tissue presents a unique scenario that may account for this difference.…”

The pattern of alternative splicing in lung adenocarcinoma shows novel events correlated with tumorigenesis and immune microenvironment

“…Its parental gene SOD2 is a crucial enzyme for scavenging ROS generated by mitochondria, which is necessary for cellular homeostasis [ 49 ]. Reported studies have been revealed that SOD2 has been linked with the energy metabolism of colorectal cancer [ 50 ], oxidative stress in endocrine cancer [ 51 ], and stem cell reprogramming in breast cancer [ 52 ]. Other parental genes in the two signatures, in addition to this one, have been identified to perform a considerable task in the existence and progression of many cancers to differing degrees, as well as the prognosis of cancer patients.…”

Clinical significance and potential mechanisms of miR-223-3p and miR-204-5p in squamous cell carcinoma of head and neck: a study based on TCGA and GEO

“…It may be a novel angle to elucidate the pathogenesis of SCCHN from the perspective of miR-223-3p regulating the EMT. Analyses also suggested that miR-223-3p and miR-204-5p may affect the energy balance of SCCHN through AMPK signaling pathway, a proved regulatory signaling pathway for the energy metabolism of tumors [44][45][46][47]. Energy metabolism plays important roles in cancer progression and the regulation of energy metabolism balance may become one of the effective anti-tumor treatment methods [48,49].…”