Abstract
Tumor migration and invasion are key pathological processes that contribute to cell metastasis as well as treatment failure in patients with malignant tumors. However, the mechanisms governing tumor cell migration remain poorly understood. By analyzing the tumor-related database and tumor cell lines, we found that preoptic regulatory factor-2 (Porf-2) is downexpressed in both neuroblastoma and glioma. Using in vitro assays, our data demonstrated that the expression of Porf-2 inhibits tumor cell migration both in neuroblastoma and glioma cell lines. Domain-mutated Porf-2 plasmids were then constructed, and it was found that the GAP domain, which plays a role in the inactivation of Rac1, is the functional domain for inhibiting tumor cell migration. Furthermore, by screening potential downstream effectors, we found that Porf-2 can reduce MMP-2 and MMP-9 expression. Overexpression of MMP-2 blocked the inhibitory effect of Porf-2 in tumor cell migration both in vitro and in vivo. Taken together, we show for the first time that Porf-2 is capable of suppressing tumor cell migration via its GAP domain and the downregulation of MMP-2/9, suggesting that targeting Porf-2 could be a promising therapeutic strategy for nervous system tumors.
Highlights
Tumor migration and invasion are a hallmark of most human cancers and remain a major source of treatment failure in patients with malignant tumors [1, 2]
Our analysis revealed that preoptic regulatory factor-2 (Porf-2) is downregulated in glioma, acute myeloid leukemia, testicular germ cell tumors, and thyroid carcinoma, while it is unregulated in bladder urothelial carcinoma, breast invasive carcinoma and several other tumors (Figure 1A)
As Porf-2 is reported to be highly expressed in the nervous system, such as brain and ganglion [14], we focused on its involvement in nervous system tumors, especially glioma and neuroblastoma
Summary
Tumor migration and invasion are a hallmark of most human cancers and remain a major source of treatment failure in patients with malignant tumors [1, 2]. Despite recent advances in standard therapy, including surgical resection followed by radiation and chemotherapy, the prognosis for patients with malignant glioma and neuroblastoma remains dismal due to the highly proliferative, migratory, and invasive capacity of tumor cells [3,4,5,6,7,8]. Numerous studies have attempted to elucidate the molecular mechanisms of tumor migration in recent years, the results are not satisfactory. There is an urgent need to investigate the molecular mechanisms underpinning tumor cell migration
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