The interaction of PRDX1 with Cofilin promotes oral squamous cell carcinoma metastasis

Peroxiredoxin 1 (PRDX1) is an important member of the peroxiredoxin family (PRDX) and is upregulated in a variety of tumors. Previous studies have found that high PRDX1 expression is closely related to the metastasis of oral squamous cell carcinoma (OSCC), but the specific molecular mechanism is elusive. To elucidate the role of PRDX1 in the metastasis process of OSCC, we evaluated the expression of PRDX1 in OSCC clinical specimens and its impact on the prognosis of OSCC patients. Then, the effect of PRDX1 on OSCC metastasis and cytoskeletal reconstruction was explored in vitro and in nude mouse tongue cancer models, and the molecular mechanisms were also investigated. PRDX1 can directly interact with the actin-binding protein Cofilin, inhibiting the phosphorylation of its Ser3 site, accelerating the depolymerization and turnover of actin, promoting OSCC cell movement, and aggravating the invasion and metastasis of OSCC. In clinical samples and mouse tongue cancer models, PRDX1 also increased lymph node metastasis of OSCC and was negatively correlated with the phosphorylation of Cofilin; PRDX1 also reduced the overall survival rate of OSCC patients. In summary, our study identified that PRDX1 may be a potential therapeutic target to inhibit OSCC metastasis. Stress-induced expression of peroxiredoxin 1 (PRDX1) is suspected of facilitating the progression of oral squamous cell carcinoma (OSCC). The role of PRDX1 in OSCC, however, remains uncertain. Here, the authors investigated the effect of PRDX1 on OSCC progression via cytoskeletal remodeling, a process fundamental to tumor metastasis. Analyses show that PRDX1 interacts with Cofilin, specifically inhibiting serine 3 phosphorylation. In a tongue cancer xenograft mouse model, these effects were found to promote cytoskeletal reconstruction and to accelerate cell migration. The findings identify a contributory role for PRDX1 in OSCC progression and highlight PRDX1 as a potential therapeutic target. image