Zhang Ke-Jing, Tan Xiao-Lang, Guo Lei
Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, P.R. China.
Clinical Research Center for Breast Cancer in Hunan Province, Changsha, Hunan Province 410008, P.R. China.
iScience. 2023 Aug 7;26(9):107556. doi: 10.1016/j.isci.2023.107556. eCollection 2023 Sep 15.
The focus of the study is to examine the function of TYMSOS in immune escape of breast cancer, which is the most frequently diagnosed malignancy among women globally. Our study demonstrated that upregulated TYMSOS was associated with unfavorable prognosis and immune escape in breast cancer. TYMSOS promoted the malignant phenotypes of breast cancer cells, and reduced the cytotoxicity of NK92 cells on these cells. CBX3 was a downstream effector in TYMSOS-induced malignant phenotypes in breast cancer cells. Mechanistic studies showed that TYMSOS facilitated CBX3-mediated transcriptional repression of ULBP3, and it also promoted SYVN1-mediated ubiquitin-proteasomal degradation of ULBP3. TYMSOS promoted cell growth, metastasis, and immune escape via CBX3/ULBP3 or SYVN1/ULBP3 axis. The studies further showed that silencing of TYMSOS repressed tumor growth and boosted NK cell cytotoxicity. In sum, TYMSOS boosted breast cancer metastasis and immune escape via CBX3/ULBP3 or SYVN1/ULBP3 axis.
该研究的重点是检测TYMSOS在乳腺癌免疫逃逸中的作用，乳腺癌是全球女性中最常被诊断出的恶性肿瘤。我们的研究表明，TYMSOS上调与乳腺癌的不良预后和免疫逃逸相关。TYMSOS促进了乳腺癌细胞的恶性表型，并降低了NK92细胞对这些细胞的细胞毒性。CBX3是TYMSOS诱导的乳腺癌细胞恶性表型中的下游效应因子。机制研究表明，TYMSOS促进了CBX3介导的ULBP3转录抑制，并且还促进了SYVN1介导的ULBP3泛素-蛋白酶体降解。TYMSOS通过CBX3/ULBP3或SYVN1/ULBP3轴促进细胞生长、转移和免疫逃逸。研究进一步表明，沉默TYMSOS可抑制肿瘤生长并增强NK细胞的细胞毒性。总之，TYMSOS通过CBX3/ULBP3或SYVN1/ULBP3轴促进乳腺癌转移和免疫逃逸。
