Transmembrane 4 L Six Family Member 1 Suppresses Hormone Receptor--Positive, HER2-Negative Breast Cancer Cell Proliferation.
Transmembrane 4 L Six Family Member 1 Suppresses Hormone Receptor--Positive, HER2-Negative Breast Cancer Cell Proliferation.
复制标题
跨膜 4 L 六家族成员 1 抑制激素受体 - 阳性、HER2 阴性乳腺癌细胞增殖
DOI：
10.3389/fphar.2022.770993
复制
发表时间：
2022
影响因子：
5.6
通讯作者：
Lu HS
中科院分区：
文献类型：
--
作者：
Chen J;Zhu J;Xu SJ;Zhou J;Ding XF;Liang Y;Chen G;Lu HS
背景：乳腺癌的预后因分子亚型不同而不同。跨膜蛋白4-L六个家族1(TM4SF1)在乳腺癌的分子亚型中表现出不同的表达模式。然而，TM4SF1在激素受体HR+HER2-乳腺癌中的表达谱仍不清楚。方法：通过分析肿瘤基因组图谱(TCGA)数据集，检测TM4SF1mRNA在乳腺癌主要亚类中的表达。采用免疫组织化学和Western印迹方法检测HR+HER2-乳腺癌组织中TM4SF1蛋白和mRNA的表达水平。通过四甲基偶氮唑盐比色法、集落形成法、3D类器官移植模型和异种移植模型评价TM4SF1对细胞增殖的影响。结果：TCGA数据库分析表明，TM4SF1在乳腺癌组织中的表达较正常乳腺组织下调。此外，TM4SF1在基底样癌和间叶性TNBC组织中的表达均高于癌旁正常乳腺组织。其他类型，包括腔雄激素受体阳性的TNBC组织，表达水平较低的TM4SF1。免疫组织化学和实时荧光定量聚合酶链式反应分析表明，HR+HER2-乳腺癌组织中TM4SF1蛋白和mRNA的表达水平均低于癌旁正常组织。此外，TM4SF1过表达降低了MCF-7和ZR-75-1乳腺癌细胞的活力，同时减少了这些细胞系形成的集落和3D-有机物的数量。相反，TM4SF1基因敲除导致MCF-7细胞增殖增加。然而，在TNBC细胞系中，MDA-MB-231、TM4SF1沉默抑制了细胞的增殖。在体内，TM4SF1的过表达抑制了裸鼠模型中MCF-7移植瘤的生长，这与下调Ki-67的表达、诱导细胞凋亡和抑制mTOR通路有关。结论：TM4SF1在HR+HER2-乳腺癌中表达下调，TM4SF1过表达抑制该亚型乳腺癌的细胞增殖。
Background: The prognosis of breast cancer varies according to the molecular subtype. Transmembrane 4 L six family 1 (TM4SF1) exhibits different expression patterns among the molecular subtypes of breast cancer. However, the expression profile of TM4SF1 in hormone receptor HR+HER2- breast cancer remains unclear. Methods: TM4SF1 mRNA levels were examined in major subclasses of breast cancer by analyzing The Cancer Genome Atlas (TCGA) datasets. In addition, TM4SF1 protein and mRNA levels in HR+HER2- breast cancer tissue samples were determined by immunohistochemistry and Western blot assay. The effect of TM4SF1 on cell proliferation was evaluated using MTT, colony formation, 3D organoid, and xenograft models, following the TM4SF1 overexpression or knockdown. Results: TCGA database analysis demonstrated that TM4SF1 was downregulated in breast cancer compared with the healthy adjacent breast tissue. In addition, the expression of TM4SF1 in basal-like one and the mesenchymal TNBC tissue was higher than that of the healthy adjacent breast tissue. Other types, including the luminal androgen receptor–positive TNBC tissue, expressed lower levels of TM4SF1. Immunohistochemistry and real-time quantitative PCR assays demonstrated that the TM4SF1 protein and mRNA levels were downregulated in the HR+HER2- breast cancer tissue compared with the healthy adjacent tissue. Moreover, the TM4SF1 overexpression reduced the viability of MCF-7 and ZR-75-1 breast cancer cells, whilst reducing the number of colonies and 3D-organoids formed by these cell lines. By contrast, TM4SF1 knockdown led to an increased MCF-7 cell proliferation. However, in the TNBC cell line, MDA-MB-231, TM4SF1 silencing reduced cell proliferation. In vivo, the TM4SF1 overexpression inhibited MCF-7 xenograft growth in a nude mouse model, which was associated with the downregulation of the Ki-67 expression, apoptosis induction, and inhibition of the mTOR pathway. Conclusion: TM4SF1 is downregulated in HR + HER2-breast cancer, and the overexpression of TM4SF1 suppresses cell proliferation in this cancer subtype.
登录
查看更多内容
影响因子：
11.2
作者：
Simpson NE;Lambert WM;Watkins R;Giashuddin S;Huang SJ;Oxelmark E;Arju R;Hochman T;Goldberg JD;Schneider RJ;Reiz LF;Soares FA;Logan SK;Garabedian MJ
通讯作者：
Garabedian MJ
影响因子：
5.3
作者：
Zhu C;Luo X;Wu J;Liu Y;Liu L;Ma S;Xie R;Wang S;Ji W
通讯作者：
Ji W
影响因子：
3.7
作者：
Matsuda, Satoru;Kawakubo, Hirofumi;Kitagawa, Yuko
通讯作者：
Kitagawa, Yuko
影响因子：
3.6
作者：
Lupinacci, Simona;Perri, Anna;Bonofiglio, Renzo
通讯作者：
Bonofiglio, Renzo
雌激素调节的反馈回路限制了雌激素受体靶向乳腺癌治疗的功效。
DOI：
10.1073/pnas.1722617115
发表时间：
2018-07-31
影响因子：
11.1
作者：
Xiao T;Li W;Wang X;Xu H;Yang J;Wu Q;Huang Y;Geradts J;Jiang P;Fei T;Chi D;Zang C;Liao Q;Rennhack J;Andrechek E;Li N;Detre S;Dowsett M;Jeselsohn RM;Liu XS;Brown M
通讯作者：
Brown M