Department of Gynecologic Oncology, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China.
Center of Translational Medicine, Zibo Central Hospital, Zibo, China.
Carcinogenesis. 2019 Jun 10;40(4):592-599. doi: 10.1093/carcin/bgy163.
Previous studies have shown that TIPE1 inhibits tumor proliferation and metastasis in certain cancers; however, increased expression of TIPE1 is observed in cervical cancer cell lines and tissues, indicating it might exert a distinctive role in cervical cancer. Cell and xenograft tumorigenicity assays showed that TIPE1 facilitates cervical cancer progression in this study. Further investigation demonstrated that TIPE1 binds to p53 and impairs its activity via inhibition of its acetylation. In addition, TIPE1 promoted cell proliferation and suppressed cisplatin susceptibility in a p53-dependent manner, indicating that TIPE1 facilitates cervical cancer progression primarily through the p53 pathway. TIPE1 expression in clinical samples also demonstrated that its upregulation predicts poor prognosis in patients with cervical cancer. Taken together, the results of this study showed that TIPE1 serves as an oncogene by restricting p53 activity in the development of cervical cancer, suggesting that TIPE1 will provide a new potential target for cervical cancer therapy and can be used as a biomarker to predict patient prognosis.
先前的研究表明，TIPE1 可抑制某些癌症中的肿瘤增殖和转移；然而，在宫颈癌细胞系和组织中观察到 TIPE1 的表达增加，表明其可能在宫颈癌中发挥独特作用。细胞和异种移植肿瘤发生测定表明，TIPE1 在本研究中促进了宫颈癌的进展。进一步的研究表明，TIPE1 通过抑制其乙酰化来结合 p53 并损害其活性。此外，TIPE1 以依赖于 p53 的方式促进细胞增殖并抑制顺铂敏感性，表明 TIPE1 主要通过 p53 途径促进宫颈癌的进展。临床样本中的 TIPE1 表达也表明，其上调预示着宫颈癌患者预后不良。综上所述，本研究结果表明，TIPE1 通过限制 p53 在宫颈癌发展中的活性而充当致癌基因，表明 TIPE1 将为宫颈癌治疗提供新的潜在靶点，并可用作预测患者预后的生物标志物。
