The Cancer/Testis Antigen CT45A1 Promotes Transcription of Oncogenic Sulfatase-2 Gene in Breast Cancer Cells and Is Sensible Targets for Cancer Therapy

Ping Yang; Yingnan Qiao; Huaidong Liao; Yizheng Huang; Mei Meng; Yu Chen; Quansheng Zhou

doi:10.4048/jbc.2023.26.e5

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자료유형: 학술저널

저자정보: Ping Yang (Department of Pathophysiology School of Medicine Nantong University Nantong P.R. China.) Yingnan Qiao (Cyrus Tang Hematology Center Jiangsu Institute of Hematology Soochow University Suzhou P.R. China.) Huaidong Liao (Cyrus Tang Hematology Center Jiangsu Institute of Hematology Soochow University Suzhou P.R. China.) Yizheng Huang (Department of Pathophysiology School of Medicine Nantong University Nantong P.R. China.) Mei Meng (Cyrus Tang Hematology Center Jiangsu Institute of Hematology Soochow University Suzhou P.R. China.) Yu Chen (Cyrus Tang Hematology Center Jiangsu Institute of Hematology Soochow University Suzhou P.R. China.) Quansheng Zhou (Cyrus Tang Hematology Center Jiangsu Institute of Hematology Soochow University Suzhou P.R. China.State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.26 No.2

발행연도: 2023.4

수록면: 168 - 185 (18page)

DOI: 10.4048/jbc.2023.26.e5

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Purpose: Invasive breast carcinomas (BRCAs) are highly lethal. The molecular mechanisms underlying progression of invasive BRCAs are unclear, and effective therapies are highly desired. The cancer-testis antigen CT45A1 promotes overexpression of pro-metastatic sulfatase-2 (SULF2) and breast cancer metastasis to the lungs, but its mechanisms are largely unknown. In this study, we aimed to elucidate the mechanism of CT45A1-induced SULF2 overexpression and provide evidence for targeting CT45A1 and SULF2 for breast cancer therapy. Methods: The effect of CT45A1 on SULF2 expression was assessed using reverse transcription polymerase chain reaction and western blot. The mechanism of CT45A1-induced SULF2 gene transcription was studied using protein-DNA binding assay and a luciferase activity reporter system. The interaction between CT45A1 and SP1 proteins was assessed using immunoprecipitation and western blot. Additionally, the suppression of breast cancer cell motility by SP1 and SULF2 inhibitors was measured using cell migration and invasion assays. Results: CT45A1 and SULF2 are aberrantly overexpressed in patients with BRCA; importantly, overexpression of CT45A1 is closely associated with poor prognosis. Mechanistically, gene promoter demethylation results in overexpression of both CT45A1 and SULF2. CT45A1 binds directly to the core sequence GCCCCC in the promoter region of SULF2 gene and activates the promoter. Additionally, CT45A1 interacts with the oncogenic master transcription factor SP1 to drive SULF2 gene transcription. Interestingly, SP1 and SULF2 inhibitors suppress breast cancer cell migration, invasion, and tumorigenicity. Conclusion: Overexpression of CT45A1 is associated with poor prognosis in patients with BRCA. CT45A1 promotes SULF2 overexpression by activating the promoter and interacting with SP1. Additionally, SP1 and SULF2 inhibitors suppress breast cancer cell migration, invasion, and tumorigenesis. Our findings provide new insight into the mechanisms of breast cancer metastasis and highlight CT45A1 and SULF2 as sensible targets for developing novel therapeutics against metastatic breast cancer.

#Breast Neoplasms #Carcinogenesis #Prognosis #Proto-Oncogenes #Sulfatases

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