FSIP1促进乳腺癌细胞迁移和侵袭并导致患者不良预后

doi:10.11904/j.issn.1002-3070.2022.03.007

摘要/Abstract

摘要： 目的探讨乳腺癌组织中纤维鞘相互作用蛋白1(FSIP1)表达对乳腺癌细胞侵袭和迁移能力的影响及其与乳腺癌患者预后的关系,从而为乳腺癌的诊断和治疗提供一定的理论参考。方法收集2004年1月—2018年12月于哈尔滨医科大学附属肿瘤医院确诊的404例乳腺癌患者的乳腺组织样本和病例资料,对收集的乳腺癌患者资料进行回顾性分析并采用Kaplan-Meier方法绘制生存曲线,采用免疫组织化学方法分析FSIP1在乳腺癌和癌旁组织中的表达情况,取乳腺癌细胞系MCF-7、MDA-MB-231、MDA-MB-435、SK-BR-3、T-47D及正常乳腺上皮细胞(HMECs)MCF-10A进行细胞培养,采用CRISPR/CAS9技术敲除乳腺癌细胞系MDA-MB-231和SK-BR-3中的FSIP1基因,通过Western blot实验检测各乳腺癌细胞系中FSIP1蛋白的表达情况并对FSIP1基因敲除结果进行检测,通过细胞迁移和侵袭实验评估FSIP1蛋白敲除对乳腺癌细胞迁移和侵袭能力的影响。结果与正常乳腺上皮细胞(MCF-10A)相比,乳腺癌细胞系MCF-7、MDA-MB-231、MDA-MB-435、SK-BR-3、T-47D中FSIP1的表达水平均显著升高(P＜0.01);与癌旁乳腺组织相比,乳腺癌组织中FSIP1的表达水平显著升高(P＜0.01);生存分析结果显示,FSIP1表达水平较高的乳腺癌患者总生存期显著缩短(P＜0.001),且FSIP1的表达水平与乳腺癌患者的临床分期(P=0.006)及细胞增殖标记物Ki-67(P=0.0067)表达相关;迁移实验和侵袭实验结果显示,敲除FSIP1基因后乳腺癌细胞系MDA-MB-231和SK-BR-3的迁移和侵袭能力显著降低(P＜0.01)。结论 FSIP1在乳腺癌细胞中高表达能够增强其迁移和侵袭能力,并与患者预后不良相关。

关键词: 纤维鞘相互作用蛋白1, 乳腺癌, 迁移, 侵袭

Abstract: Objective The aims of this study were to investigate the effect of FSIP1 expression in breast cancer tissues on the migration and invasion ability of breast cancer cells,and its relationship with the prognosis of breast cancer patients,so as to provide certain theoretical reference for the diagnosis and treatment of breast cancer. Methods The breast tissue samples and case data of 404 breast cancer patients diagnosed in Harbin Medical University Cancer Hospital from January 2004 to December 2018 were collected.The collected data of breast cancer patients were retrospectively analyzed and the survival curve was plotted by Kaplan-Meier method.Immunohistochemistry was used to analyze the expression of FSIP1 in breast cancer and adjacent tissues,and breast cancer MCF-7,MDA-MB-231,MDA-MB-435,SK-BR-3,T-47D and HMECs(MCF-10A)cell lines were cultured.The FSIP1 gene in breast cancer MDA-MB-231 and SK-BR-3 cell lines was knocked out using CRISPR/CAS9 technology and detected by Western blot.The effect of FSIP1 gene knockout on migration and invasion abilities of breast cancer cells was evaluated through cell migration and invasion assays. Results Compared with HMECs(MCF-10A),the expression of FSIP1 in breast cancer MCF-7,MDA-MB-231,MDA-MB-435,SK-BR-3,and T-47D cell lines was significantly increased(P＜0.01).Compared with adjacent breast tissues,the expression of FSIP1 in breast cancer tissues was significantly increased(P＜0.01).Survival analysis showed that the overall survival of breast cancer patients with the high expression of FSIP1 was significantly shortened(P＜0.01).The expression of FSIP1 was correlated with the clinical stage of breast cancer(P=0.0061)and the expression of cell proliferation marker-Ki-67(P=0.0067).The results of migration and invasion experiments showed that after knocking out the FSIP1 gene,the migration and invasion capabilities of breast cancer MDA-MB-231 and SK-BR-3 cells were significantly reduced(P＜0.01). Conclusion The high expression of FSIP1 in breast cancer cells can enhance their migration and invasion capabilities,and is correlated with the poor prognosis of patients.

Key words: Fibrous sheath interacting protein 1, Breast cancer, Migration, Invasion

中图分类号:

R737.9

何伟丹, 李志高. FSIP1促进乳腺癌细胞迁移和侵袭并导致患者不良预后[J]. 实用肿瘤学杂志, 2022, 36(3): 233-238.

HE Weidan, LI Zhigao. FSIP1 promotes migration and invasion of breast cancer cells and leads to poor prognosis of patients[J]. Journal of Practical Oncology, 2022, 36(3): 233-238.

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链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2022.03.007

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2022/V36/I3/233

参考文献

1 Koual M,Tomkiewicz C,Cano-Sancho G,et al.Environmental chemicals,breast cancer progression and drug resistance[J].Environ Health,2020,19(1):117-122.
2 Andersson Y,Bergkvist L,Frisell J,et al.Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes[J].Breast Cancer Res Treat,2018,171(2):359-369.
3 Chun KH,Park JH,Fan S.Predicting and overcoming chemotherapeutic resistance in breast cancer[J].Adv Exp Med Biol,2017,1026:59-104.
4 靳团,张清媛.乳腺癌脑转移的信号通路和分子机制的研究进展[J].实用肿瘤学杂志,2017,31(5):468-471.
5 Feng Y,Wu M,Li S,et al.The epigenetically downregulated factor CYGB suppresses breast cancer through inhibition of glucose metabolism[J].J Exp Clin Cancer Res,2018,37(1):313.
6 余科达,韦光楠.70基因检测可作为制定早期乳腺癌治疗方案的辅助手段[J].循证医学,2019,19(3):142-144.
7 Steger G,Lüftner D,Stger H,et al.Management of HER2-positive early breast cancer[J].Breast Care(Basel),2018,13(6):453-455.
8 Liu T,Zhang H,Sun L,et al.FSIP1 binds HER2 directly to regulate breast cancer growth and invasiveness[J].Proc Natl Acad Sci U S A,2017,114(29):7683-7688.
9 Zhang H,Luo M,Jin Z,et al.Expression and clinicopathological significance of FSIP1 in breast cancer[J].Oncotarget,2015,6(12):10658-10666.
10 Bommer GT,Gerin I,Feng Y,et al.p53-mediated activation of miRNA34 candidate tumor-suppressor genes[J].Curr Biol,2007,17(15):1298-1307.
11 Cardoso F,Senkus E,Costa A,et al.4th ESO-ESMO international consensus guidelines for advanced breast cancer(ABC 4)+[J].Ann Oncol,2018,29(8):1634-1657.
12 Li W,Zheng X,Ren L,et al.Eipgenetic hypomethylation and upregulation of GD3s in triple negative breast cancer[J].Ann Transl Med,2019,7(23):723.
13 Grizzi G,Ghidini M,Botticelli A,et al.Strategies for increasing the effectiveness of aromatase inhibitors in locally advanced breast cancer:An evidence-based review on current options[J].Cancer Manag Res,2020,12:675-686.
14 Cappell KM,Sinnott R,Taus P,et al.Multiple cancer testis antigens function to support tumor cell mitotic fidelity[J].Mol Cell Biol,2012,32(20):4131-4140.
15 Salem AF,Whitaker-Menezes D,Howell A,et al.Mitochondrial biogenesis in epithelial cancer cells promotes breast cancer tumor growth and confers autophagy resistance[J].Cell Cycle,2012,11(22):4174-4180.
16 Liu C,Sun L,Yang J,et al.FSIP1 regulates autophagy in breast cancer[J].Proc Natl Acad Sci USA,2018,115(51):13075-13080.
17 Yousefnia S,Seyed FF,Seyed FS,et al.Mechanistic pathways of malignancy in breast cancer stem cells[J].Front Oncol,2020,10:452.
18 Abolghasemi M,Tehrani SS,Yousefi T,et al.MicroRNAs in breast cancer:roles,functions,and mechanism of actions[J].J Cell Physiol,2020,235(6):5008-5029.
19 Guo S,Deng CX.Effect of stromal cells in tumor microenvironment on metastasis initiation[J].Int J Biol Sci,2018,14(14):2083-2093.
20 Izawa Y,Kashii-Magaribuchi K,Yoshida K,et al.Stem-like human breast cancer cells initiate vasculogenic mimicry on matrigel[J].Acta Histochem Cytochem,2018,51(6):173-183.

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