Foxc2生理功能研究进展

doi:10.19438/j.cjoms.2018.02.019

中国口腔颌面外科杂志 ›› 2018, Vol. 16 ›› Issue (2): 188-192.doi: 10.19438/j.cjoms.2018.02.019

• 综述 • 上一篇

Foxc2生理功能研究进展

沈洪洲, 司家文, 沈国芳

上海交通大学医学院附属第九人民医院·口腔医学院口腔颅颌面科,上海市口腔医学重点实验室,上海市口腔医学研究所，国家口腔疾病临床研究中心，上海 200011

收稿日期:2017-03-06 修回日期:2017-06-14 出版日期:2018-03-20 发布日期:2018-04-08
通讯作者: 沈国芳,E-mail: maxillofacsurg@163.com
作者简介:沈洪洲（1991-）,男,博士,E-mail: shenhongzhou0389@163.com
基金资助:
国家自然科学基金（81570947,81600827）

Current research progress of physiological functions of Foxc2

SHEN Hong-zhou, SI Jia-wen, SHEN Guo-fang

Department of Oral and Craniomaxillofacial Science, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology; National Clinical Research Center of Stomatology. Shanghai 200011, China;

Received:2017-03-06 Revised:2017-06-14 Online:2018-03-20 Published:2018-04-08

摘要/Abstract

摘要： Foxc2属于进化上高度保守的Forkhead转录因子家族中的一员，具有典型的Forkhead结构域。Foxc2参与了胚胎发育、上皮-间充质转化、间充质组织分化、脂肪细胞代谢等众多生理过程。Foxc2基因突变或调控异常可导致一系列改变，如淋巴系统和中轴骨系统发育障碍、肿瘤形成、能量代谢异常等。因此，针对Foxc2的深入研究将有助于进一步揭示与其相关疾病的发病与发展机制。本文就近年来Foxc2生理功能的研究进展进行综述。

关键词: Foxc2, 生理功能, 间充质组织

Abstract: Foxc2, one of the family members of the evolutionarily highly conserved Forkhead transcription factors, possesses a classical Forkhead domain. Foxc2 has been shown to be involved in various physiological processes including embryonic development, epithelial-to-mesenchymal transition, differentiation of mesenchymal tissue and adipocyte metabolism. Mutations or abnormal regulation of Foxc2 gene could lead to a series of changes, such as developmental disorders of lymphatic system and axial bones, tumorgenesis, aberrant energetic metabolism, and etc. Thus, it seems that thorough research about Foxc2 might further unveil the pathogenesis and developmental mechanism of Foxc2-related diseases. This review mainly focused on the current research findings of physiological functions of Foxc2.

Key words: Foxc2, Physiological function, Mesenchymal tissue

中图分类号:

沈洪洲, 司家文, 沈国芳. Foxc2生理功能研究进展[J]. 中国口腔颌面外科杂志, 2018, 16(2): 188-192.

SHEN Hong-zhou, SI Jia-wen, SHEN Guo-fang. Current research progress of physiological functions of Foxc2[J]. China J Oral Maxillofac Surg, 2018, 16(2): 188-192.

参考文献

[1] 陈琦, 郑谦. 叉头框C-2基因与中轴骨骼系统的发育[J].国际口腔医学杂志, 2011, 38(3): 361-363.
[2] Mellor RH, Brice G, Stanton AW, et al.Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb[J]. Circulation, 2007, 115(14): 1912-1920.
[3] Ivanov KI, Agalarov Y, Valmu L, et al.Phosphorylation regulates FOXC2-mediated transcription in lymphatic endothelial cells[J]. Mol Cell Biol, 2013, 33(19): 3749-3761.
[4] Liebl J, Zhang S, Moser M, et al.Cdk5 controls lymphatic vessel development and function by phosphorylation of Foxc2[J]. Nat Commun, 2015, 6: 7274.
[5] Sweet DT, Jiménez JM, Chang J, et al.Lymph flow regulates collecting lymphatic vessel maturation in vivo[J]. J Clin Invest, 2015, 125(8): 2995-3007.
[6] Sabine A, Agalarov Y, Maby-El Hajjami H, et al. Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation[J]. Dev Cell, 2012, 22(2): 430-445.
[7] Sabine A, Bovay E, Demir CS, et al.FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature[J]. J Clin Invest, 2015, 125(10): 3861-3877.
[8] Cha B, Geng X, Mahamud MR, et al.Mechanotransduction activates canonical Wnt/β-catenin signaling to promote lymphatic vascular patterning and the development of lymphatic and lymphovenous valves[J]. Gene Dev, 2016, 30(12): 1454-1469.
[9] Kazenwadel J, Betterman KL, Chong CE, et al.GATA2 is required for lymphatic vessel valve development and maintenance[J]. J Clin Invest, 2015, 125(8): 2979-2994.
[10] Norrmén C, Ivanov KI, Cheng J, et al.Foxc2 controls formation and maturation of lymphatic collecting vessels through cooperation with NFATc1[J]. J Cell Biol, 2009, 185(3): 439-457.
[11] Taube JH, Herschkowitz JI, Komurov K, et al.Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes[J]. P Natl Acad Sci USA, 2010,107(35): 15449-15454.
[12] Mani SA, Yang J, Brooks M, et al.Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers[J]. P Natl Acad Sci USA, 2007, 104(24): 10069-10074.
[13] Hader C, Marlier A, Cantley L.Mesenchymal-epithelial transition in epithelial response to injury: the role of Foxc2[J]. Oncogene, 2010, 29(7): 1031-1040.
[14] Pietilä M, Vijay GV, Soundararajan R, et al.FOXC2 regulates the G2/M transition of stem cell-rich breast cancer cells and sensitizes them to PLK1 inhibition[J]. Sci Rep, 2016, 6: 23070.
[15] Hollier BG, Tinnirello AA, Werden SJ, et al.FOXC2 expression links epithelial-mesenchymal transition and stem cell properties in breast cancer[J]. Cancer Res, 2013, 73(6): 1981-1992.
[16] Sarkar TR, Battula VL, Werden SJ, et al.GD3 synthase regulates epithelial-mesenchymal transition and metastasis in breast cancer[J]. Oncogene, 2015, 34(23): 2958-2967.
[17] Wang QS, Kong PZ, Li XQ, et al.FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer[J]. Breast Cancer Res, 2015, 17: 30.
[18] Cai J, Tian AX, Wang QS, et al.FOXF2 suppresses the FOXC2-mediated epithelial-mesenchymal transition and multidrug resistance of basal-like breast cancer[J]. Cancer Lett, 2015, 367(2): 129-137.
[19] Golden D, Cantley LG.Casein kinase 2 prevents mesenchymal transformation by maintaining Foxc2 in the cytoplasm[J]. Oncogene, 2015, 34(36): 4702-4712.
[20] Ji X, Lu H, Zhou Q, et al.LARP7 suppresses P-TEFb activity to inhibit breast cancer progression and metastasis[J]. Elife, 2014, 3: e02907.
[21] Johansson AC, La Fleur L, Melissaridou S, et al.The relationship between EMT, CD44(high) /EGFR(low) phenotype, and treatment response in head and neck cancer cell lines[J]. J Oral Pathol Med, 2016, 45(9): 640-646.
[22] Li YC, Chang JT, Chiu C, et al.Areca nut contributes to oral malignancy through facilitating the conversion of cancer stem cells[J]. Mol Carcinogen, 2016, 55(5): 1012-1023.
[23] Imayama N, Yamada SI, Yanamoto S, et al.FOXC2 expression is associated with tumor proliferation and invasion potential in oral tongue squamous cell carcinoma[J]. Pathol Oncol Res, 2015, 21(3): 783-791.
[24] Ferrara N.Pathways mediating VEGF-independent tumor angiogenesis[J]. Cytokine Growth Factor Rev, 2010, 21(1): 21-26.
[25] Danciu TE, Chupreta S, Cruz O, et al.Small ubiquitin-like modifier (SUMO) modification mediates function of the inhibitory domains of developmental regulators FOXC1 and FOXC2[J]. J Biol Chem, 2012, 287(22): 18318-18329.
[26] Sasahira T, Ueda N, Yamamoto K, et al.Prox1 and FOXC2 act as regulators of lymphangiogenesis and angiogenesis in oral squamous cell carcinoma[J]. PloS One, 2014, 9(3): e92534.
[27] He F, Hu X, Xiong W, et al.Directed Bmp4 expression in neural crest cells generates a genetic model for the rare human bony syngnathia birth defect[J]. Dev Biol, 2014, 391(2): 170-181.
[28] Ozturk F, Li Y, Zhu X, et al.Systematic analysis of palatal transcriptome to identify cleft palate genes within TGFβ3-knockout mice alleles: RNA-Seq analysis of TGFβ3 Mice[J]. BMC genomics, 2013, 14: 113.
[29] Gozo MC, Aspuria PJ, Cheon DJ, et al.Foxc2 induces Wnt4 and Bmp4 expression during muscle regeneration and osteogenesis[J]. Cell Death Differ, 2013, 20(8): 1031-1042.
[30] You W, Fan L, Duan D, et al.Foxc2 over-expression in bone marrow mesenchymal stem cells stimulates osteogenic differentiation and inhibits adipogenic differentiation[J]. Mol Cell Biochem, 2014, 386(1-2): 125-134.
[31] Kim SH, Cho KW, Choi HS, et al.The forkhead transcription factor Foxc2 stimulates osteoblast differentiation[J]. Biochem Biophys Res Commun, 2009, 386(3): 532-536.
[32] Cederberg A, Grenning LM, Ahrén B, et al.FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance[J]. Cell, 2001, 106(5): 563-573.
[33] Gan L, Liu Z, Jin W, et al.Foxc2 enhances proliferation and inhibits apoptosis through activating Akt/mTORC1 signaling pathway in mouse preadipocytes[J]. J Lipid Res, 2015, 56(8): 1471-1480.
[34] Yao Y, Suraokar M, Darnay BG, et al. BSTA promotes mTORC2-Mediated phosphorylation of Akt1 to suppress expression of FoxC2 and stimulate adipocyte differentiation[J]. Sci Signal, 2013, 6 (257): ra2.
[35] Lidell ME, Seifert EL, Westergren R, et al.The adipocyte-expressed forkhead transcription factor Foxc2 regulates metabolism through altered mitochondrial function[J]. Diabetes, 2011, 60(2): 427-435.
[36] Zhang J, Zhang Y, Sun T, et al.Dietary obesity-induced Egr-1 in adipocytes facilitates energy storage via suppression of FOXC2[J]. Sci Rep, 2013, 3: 1476.

Foxc2生理功能研究进展

Current research progress of physiological functions of Foxc2

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 0

编辑推荐

Metrics

本文评价