Abstract 5998: Peroxiredoxin IV promotes progression of colorectal cancer

Abstract

Abstract Peroxiredoxin IV (Prx4) is a multifunction enzyme with a primary antioxidant role of reducing free radicals such as hydrogen peroxide and peroxynitrite. Literature review suggests that Prx4 upregulation in colorectal cancer is associated with higher tumor metastasis and shorter survival of patients. However, the function and mechanisms of Prx4 in cancer development are not well understood. The goal of this study is to validate the oncogenic role of Prx4 and to identify potential mechanisms of invasion and metastasis. Western Blot was performed to compare the expression of Prx4 protein in a normal colon cell line and seven colorectal cancer cell lines. shRNA mediated knockdown of Prx4 was performed in cancer cell lines with higher expression of Prx4. Stable vector control and Prx4 knockdown cells were used to perform Scratch Wound healing assay to compare the rate of migration. Transwell Matrigel invasion assay was performed using the same cell lines with 10% FBS containing-medium as chemoattractant. Vector control and Prx4 knockdown HCT116 cells were orthotopically implanted into the cecum wall of immunodeficient mice and humanely euthanized four weeks later. Prx4 expression is upregulated in colorectal cancer cell lines compared to normal colon cell line NCM356. Stable knockdown of Prx4 in HCT116 and RKO cell lines resulted in a significant decrease in migration and invasion rates of cancer cell lines in vitro compared to vector control. Orthotopic implantation of HCT116 vector control and Prx4 knockdown cells into cecum wall resulted in a lower metastasis rate to the liver and the lungs. We are currently conducting mechanistic studies to determine how the loss of Prx4 leads to a decrease in malignancy of colorectal cancer cell lines. Prx4 promotes colorectal cancer cell invasion and metastasis. Our study suggests Prx4 is a critical oncogenic protein that can be used as a therapeutic target for patients. This work was partially supported by the National Institutes of Health R01CA222596, Molecular Mechanisms of Toxicity Training Grant in Toxicology (T32ES07266), and American Cancer Society RSG-16-213-01-TBE. Citation Format: Pratik Thapa, Hong Jiang, Yanning Hao, Na Ding, Aziza Alshahrani, Yekaterina Zaytseva, Qiou Wei. Peroxiredoxin IV promotes progression of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5998.