-
摘要: 作为调节性T细胞中最重要的转录因子，转录因子叉头蛋白（forkheadbox protein 3，FOXP3）在T细胞研究领域已被广泛关注。然而最新研究表明，FOXP3在多种肿瘤组织中均有表达，在不同肿瘤中的表达量及发挥的功能亦不相同，部分肿瘤中FOXP3作为抑癌基因抑制肿瘤的增殖与转移，部分肿瘤中则作为癌基因促进肿瘤免疫逃逸。本文总结了FOXP3在不同肿瘤组织中的表达情况及其功能，旨在为今后FOXP3的研究和靶向治疗提供依据。Abstract: As the most important transcription factor in regulatory T cells, forkheadbox protein 3 (FOXP3) has been extensively investigated in T cells. However, FOXP3, a tumor type-dependent transcription factor, is expressed at different levels in different tumors. In some tumors, FOXP3, as a suppressor, inhibits proliferation and metastasis. In other tumors, FOXP3, as an oncogene, mediates tumor immune escape. In this review, we summarize the expression levels and functions of FOXP3 in different tumor types to provide evidence for further research.
-
Key words:
- cancer /
- transcription factor /
- FOXP3 /
- oncogene /
- tumor suppressor gene
-
表 1 FOXP3在不同肿瘤中的表达、作用及相关分子
Table 1. Expression and function of cancer-FOXP3 in different human tumors with relevant molecules and pathways
-
[1] Sakaguchi S, Yamaguchi T, Nomura T, et al. Regulatory T cells and immune tolerance[J]. Cell, 2008, 133(5):775-787. doi: 10.1016/j.cell.2008.05.009 [2] Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3[J]. Nat Genet, 2001, 27(1):20-21. doi: 10.1038/83713 [3] Lopes JE, Torgerson TR, Schubert LA, et al. Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressor[J]. J Immunol, 2006, 177(5):3133-3142. doi: 10.4049/jimmunol.177.5.3133 [4] Vadasz Z, Toubi E. FoxP3 expression in macrophages, cancer, and B cells-is it real[J]. Clin Rev Allergy Immunol, 2016, 52(3):364-372. doi: 10.1007/s12016-016-8572-5 [5] Jiang LL, Ruan LW. Association between FOXP3 promoter polymorphisms and cancer risk: a meta-analysis[J]. Oncol Lett, 2014, 8(6): 2795-2799. https://www.spandidos-publications.com/ol/8/6/2795 [6] Wang X, Lang M, Zhao T, et al. Cancer-FOXP3 directly activated CCL5 to recruit FOXP3+ Treg cells in pancreatic ductal adenocarcinoma[J]. Oncogene, 2016, doi: 10.1038/onc.2016.458. [7] Hinz S, Pagerols-Raluy L, Oberg HH, et al. Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer[J]. Cancer Res, 2007, 67(17):8344-8350. doi: 10.1158/0008-5472.CAN-06-3304 [8] Zuo T, Wang L, Morrison C, et al. FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene[J]. Cell, 2007, 129(7):1275-1286. doi: 10.1016/j.cell.2007.04.034 [9] Merlo A, Casalini P, Carcangiu ML, et al. FOXP3 expression and overall survival in breast cancer[J]. J Clin Oncol, 2009, 27(11):1746-1752. doi: 10.1200/JCO.2008.17.9036 [10] Lopes LF, Guembarovski RL, Guembarovski AL, et al. FOXP3 transcription factor: a candidate marker for susceptibility and prognosis in triple negative breast cancer[J]. Biomed Res Int, 2014, (2014): 341654. https://www.hindawi.com/journals/bmri/2014/341654/ [11] Ladoire S, Arnould L, Mignot G, et al. Presence of Foxp3 expression in tumor cells predicts better survival in HER2-overexpressing breast cancer patients treated with neoadjuvant chemotherapy[J]. Breast Cancer Res Treat, 2011, 125(1):65-72. doi: 10.1007/s10549-010-0831-1 [12] Li W, Wang L, Katoh H, et al. Identification of a tumor suppressor relay between the FOXP3 and the Hippo pathways in breast and prostate cancers[J]. Cancer Res, 2011, 71(6):2162-2171. doi: 10.1158/0008-5472.CAN-10-3268 [13] Liu R, Liu C, Chen D, et al. FOXP3 controls an miR-146/NF-kappaB negative feedback loop that inhibits apoptosis in breast cancer cells [J]. Cancer Res, 2015, 75(8):1703-1713. doi: 10.1158/0008-5472.CAN-14-2108 [14] Zhang C, Xu Y, Hao Q, et al. FOXP3 suppresses breast cancer metastasis through downregulation of CD44[J]. Int J Cancer, 2015, 137(6): 1279-1290. doi: 10.1002/ijc.29482 [15] Douglass S, Meeson AP, Overbeck-Zubrzycka D, et al. Breast cancer metastasis: demonstration that FOXP3 regulates CXCR4 expression and the response to CXCL12[J]. J Pathol, 2014, 234(1):74-85. doi: 10.1002/path.2014.234.issue-1 [16] Wang L, Liu R, Li W, et al. Somatic single hits inactivate the X-linked tumor suppressor FOXP3 in the prostate[J]. Cancer Cell, 2009, 16(4): 336-346. doi: 10.1016/j.ccr.2009.08.016 [17] Liu R, Yi B, Wei S, et al. FOXP3-miR-146-NF-kappaB Axis and Therapy for Precancerous Lesions in Prostate[J]. Cancer Res, 2015, 75(8):1714-1724. doi: 10.1158/0008-5472.CAN-14-2109 [18] Santio NM, Salmela M, Arola H, et al. The PIM1 kinase promotes prostate cancer cell migration and adhesion via multiple signalling pathways[J]. Exp Cell Res, 2016, 342(2):113-124. doi: 10.1016/j.yexcr.2016.02.018 [19] Ma GF, Chen SY, Sun ZR, et al. FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway[J]. Biochem Biophys Res Commun, 2013, 430(2):804-809. doi: 10.1016/j.bbrc.2012.11.065 [20] Ma GF, Miao Q, Liu YM, et al. High FoxP3 expression in tumour cells predicts better survival in gastric cancer and its role in tumour microenvironment[J]. Br J Cancer, 2014, 110(6):1552-1560. doi: 10.1038/bjc.2014.47 [21] Suh JH, Won KY, Kim GY, et al. Expression of tumoral FOXP3 in gastric adenocarcinoma is associated with favorable clinicopathological variables and related with Hippo pathway[J]. Int J Clin Exp Pathol, 2015, 8(11):14608-14618. https://www.ncbi.nlm.nih.gov/pubmed/?term=Expression+of+tumoral+FOXP3+in+gastric+adenocarcinoma+is+associated+with+favorable+clinicopathological+variables+and+related+with+Hippo+pathway [22] Hao Q, Zhang C, Gao Y, et al. FOXP3 inhibits NF-kappaB activity and hence COX2 expression in gastric cancer cells[J]. Cell Signal, 2014, 26(3):564-569. doi: 10.1016/j.cellsig.2013.11.030 [23] Ma C, Peng C, Lu X, et al. Downregulation of FOXP3 inhibits invasion and immune escape in cholangiocarcinoma[J]. Biochem Biophys Res Commun, 2015, 458(2):234-239. doi: 10.1016/j.bbrc.2015.01.067 [24] Gerber AL, Munst A, Schlapbach C, et al. High expression of FOXP3 in primary melanoma is associated with tumour progression[J]. Br J Dermatol, 2014, 170(1):103-109. doi: 10.1111/bjd.2014.170.issue-1 [25] Tan B, Anaka M, Deb S, et al. FOXP3 over-expression inhibits melanoma tumorigenesis via effects on proliferation and apoptosis[J]. Oncotarget, 2014, 5(1):264-276. http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=1600&path%5B%5D=1858 [26] Tan B, Behren A, Anaka M, et al. FOXP3 is not mutated in human melanoma[J]. Pigment Cell Melanoma Res, 2012, 25(3):398-400. doi: 10.1111/pcr.2012.25.issue-3 [27] Li Y, Li D, Yang W, et al. Overexpression of the transcription factor FOXP3 in lung adenocarcinoma sustains malignant character by promoting G1/S transition gene CCND1[J]. Tumour Biol, 2016, 37(6):7395-7404. doi: 10.1007/s13277-015-4616-3 [28] Fu HY, Li C, Yang W, et al. FOXP3 and TLR4 protein expression are correlated in non-small cell lung cancer: implications for tumor progression and escape[J]. Acta Histochem, 2013, 115(2):151-157. doi: 10.1016/j.acthis.2012.06.002 [29] Grimmig T, Kim M, Germer CT, et al. The role of FOXP3 in disease progression in colorectal cancer patients[J]. Oncoimmunology, 2013, 2(6):e24521. doi: 10.4161/onci.24521 [30] Ganapathi SK, Beggs AD, Hodgson SV, et al. Expression and DNA methylation of TNF, IFNG and FOXP3 in colorectal cancer and their prognostic significance[J]. Br J Cancer, 2014, 111(8):1581-1589. doi: 10.1038/bjc.2014.477 [31] Luo Q, Zhang S, Wei H, et al. Roles of Foxp3 in the occurrence and development of cervical cancer[J]. Int J Clin Exp Pathol, 2015, 8(8): 8717-8730. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4583848/ [32] Huang C, Zhou L, Chang X, et al. B7-H3, B7-H4, Foxp3 and IL-2 expression in cervical cancer: Associations with patient outcome and clinical significance[J]. Oncol Rep, 2016, 35(4):2183-2190. doi: 10.3892/or.2016.4607 [33] Zeng C, Yao Y, Jie W, et al. Up-regulation of Foxp3 participates in progression of cervical cancer[J]. Cancer Immunol Immunother, 2013, 62(3):481-487. doi: 10.1007/s00262-012-1348-8 [34] Song JJ, Zhao SJ, Fang J, et al. Foxp3 overexpression in tumor cells predicts poor survival in oral squamous cell carcinoma[J]. BMC Can-cer, 2016, (16):530. doi: 10.1186/s12885-016-2419-6 [35] Weller P, Bankfalvi A, Gu X, et al. The role of tumour Foxp3 as prognostic marker in different subtypes of head and neck cancer[J]. Eur J Cancer, 2014, 50(7):1291-1300. doi: 10.1016/j.ejca.2014.02.016 [36] Cunha LL, Morari EC, Nonogaki S, et al. Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas[J]. Clinics (Sao Paulo), 2012, 67(5):483-488. doi: 10.6061/clinics [37] Chu R, Liu SY, Vlantis AC, et al. Inhibition of Foxp3 in cancer cells induces apoptosis of thyroid cancer cells[J]. Mol Cell Endocrinol, 2015, (399):228-234. http://www.sciencedirect.com/science/article/pii/S0303720714003177 [38] Winerdal ME, Marits P, Winerdal M, et al. FOXP3 and survival in urinary bladder cancer[J]. BJU Int, 2011, 108(10):1672-1678. doi: 10.1111/j.1464-410X.2010.10020.x [39] Szylberg L, Karbownik D, Marszalek A. The Role of FOXP3 in Human Cancers[J]. Anticancer Res, 2016, 36(8):3789-3794. http://ar.iiarjournals.org/content/36/8/3789.full -
点击查看大图
表(1)
计量
- 文章访问数: 81
- HTML全文浏览量: 136
- PDF下载量: 3
- 被引次数: 0
下载:
