PLOD家族在肿瘤中的研究进展

摘要
图/表
参考文献(26)
相关文章 (15)

全文: PDF (667 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要前胶原-赖氨酸、2-酮戊二酸5-双加氧酶（PLOD）家族包含PLOD1、PLOD2和PLOD3三个成员，分别编码赖氨酸羟化酶1（LH1）、LH2和LH3，主要作用是通过催化前胶原分子翻译后的赖氨酸残基羟化促进胶原的成熟和分泌。PLOD家族蛋白表达主要受低氧诱导因子-1α、转化生长因子-β1等因子调控，不仅参与胶原成熟和细胞外基质重塑，还能诱导上皮-间质转化，在肿瘤发生发展中发挥重要作用。本文拟就PLOD的结构特点、调控因素、功能及在肿瘤进展中的作用进行综述。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	王安琪1
	2 刘云鹏1
	2 卢文卿1
	2 郑春雷1
	2 车晓芳1
	2

关键词 ：赖氨酸羟化酶, 胶原, 肿瘤, 转移

Abstract：The procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family includes three members, PLOD1, PLOD2 and PLOD3, and encodes lysine hydroxylase 1 (LH1), LH2 and LH3, respectively. The main role of PLOD is to promote collagen maturation and secretion by catalyzing the hydroxylation on lysine residues of procollagen. The expression of PLODs is mainly regulated by HIF-1, TGFβ-1 and so on. PLODs not only can promote collagen maturation and extracellular matrix remodeling, but also can induce epithelial mesenchymal transformation and can play vital role in tumorigenesis and development. This paper reviews the structural features, regulatory factors, functions of PLOD and its role in tumor progression.

Key words： Lysyl hydroxylase Collagen Tumor Metastasis

基金资助:国家重点研发计划（2017YFC1308900）；
留学人员科技活动项目择优资助项目（项目启动类）。

通讯作者: 车晓芳（1973.2-），女，博士，副研究员；研究方向：肿瘤微环境。

引用本文:

王安琪1,2 刘云鹏1,2 卢文卿1,2 郑春雷1,2 车晓芳1,2. PLOD家族在肿瘤中的研究进展[J]. 中国医药导报, 2019, 16(24): 29-31,39.
WANG Anqi1,2 LIU Yunpeng1,2 LU Wenqing1,2 ZHENG Chunlei1,2 CHE Xiaofang1,2. Research progress on PLOD family in tumor. 中国医药导报, 2019, 16(24): 29-31,39.

链接本文:

http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2019/V16/I24/29

[1] Gjaltema RA，van der Stoel MM，Boersema M，et al. Disentangling mechanisms involved in collagen pyridinoline cross-linking：The immunophilin FKBP65 is critical for dimerization of lysyl hydroxylase 2 [J]. Proc Natl Acad Sci U S A，2016，113（26）：7142-7147.
[2] Shao S，Zhang X，Duan L. Lysyl Hydroxylase Inhibition by Minoxidil Blocks Collagen Deposition and Prevents Pulmonary Fibrosis via TGF-β1/Smad3 Signaling Pathway [J]. Med Sci Monit，2018，24：8592-8601.
[3] Chen Y，Guo H，Terajima M，et al. Lysyl Hydroxylase 2 Is Secreted By Tumor Cells and Can Modify Collagen in the Extracellular Space [J]. J Biol Chem，2016，291（50）：25 799-25 808.
[4] Qi Y，Xu R. Roles of PLODs in Collagen Synthesis and Cancer Progression [J]. Front Cell Dev Biol，2018，6：66. doi：10.3389/fcell.2018.00066. eCollection 2018.
[5] Scietti L，Chiapparino A，De Giorgi F. Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3 [J]. Nat Commun，2018，9（1）：3163.
[6] Song Y，Zheng S，Wang J，et al. Hypoxia-induced PLOD2 promotes proliferation，migration and invasion via PI3K/Akt signaling in glioma [J]. Oncotarget，2017，8（26）：41 947-41 962.
[7] Gilkes DM，Bajpai S，Wong CC，et al. Procollagen lysyl hydroxylase 2 is essential for hypoxia-induced breast cancer metastasis [J]. Mol Cancer Res，2013，11（5）：456-466.
[8] Gjaltema RA，de Rond S，Rots MG，et al. Procollagen Lysyl Hydroxylase 2 Expression Is Regulated by an Alternative Downstream Transforming Growth Factor β-1 Activation Mechanism [J]. J Biol Chem，2015，290（47）：28 465-28 476.
[9] Remst DF，Blaney Davidson EN，Vitters EL，et al. TGF-β induces Lysyl hydroxylase 2b in human synovial osteoarthritic fibroblasts through ALK5 signaling [J]. Cell TissueRes，2014，355（1）：163-171.
[10] Mia MM，Bank RA. The IκB kinase inhibitor ACHP strongly attenuates TGFβ1-induced myofibroblast formation and collagen synthesis [J]. J Cell Mol Med，2015，19（12）：2780-2792.
[11] Simard A，Di Giorgio L，Amen M，et al. The Pitx2c N-terminal domain is a critical interaction domain required for asymmetric morphogenesis [J]. Dev Dyn，2009，238（10）：2459-2470.
[12] Du H，Chen Y，Hou X，et al. PLOD2 regulated by transcription factor FOXA1 promotes metastasis in NSCLC [J]. Cell Death Dis，2017，8（10）：e3143.
[13] Chen Y，Terajima M，Yang Y，et al. Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma [J]. J Clin Invest，2015，125（3）：1147-1162.
[14] Miyamoto K，Seki N，Matsushita R，et al. Tumour-suppressive miRNA-26a-5p and miR-26b-5p inhibit cell aggressiveness by regulating PLOD2 in bladder cancer [J]. Br J Cancer，2016，115（3）：354-363.
[15] Amodio G，Sasso E，D'Ambrosio C，et al. Identification of a microRNA （miR-663a） induced by ER stress and its target gene PLOD3 by a combined microRNome and proteome approach [J]. Cell Biol Toxicol，2016，32（4）：285-303.
[16] Takaluoma K，Lantto J，Myllyharju J. Lysyl hydroxylase 2 is a specific telopeptide hydroxylase，while all three isoenzymes hydroxylate collagenous sequences [J]. Matrix Biol，2007，26（5）：396-403.
[17] van der Slot AJ，Zuurmond AM，van den Bogaerdt AJ，et al. Increased formation of pyridinoline cross-links due to higher telopeptide lysyl hydroxylase levels is a general fibrotic phenomenon [J]. Matrix Biol，2004，23（4）：251-257.
[18] Dayer C，Stamenkovic I. Recruitment of Matrix Metalloproteinase-9（MMP-9）to the Fibroblast Cell Surface by Lysyl Hydroxylase3 （LH3） Trigger Transforming Growth Factor-β（TGF-β）Activation and Fibroblast Differentiation [J]. J Biol Chem，2015，290（22）：13 763-13 778.
[19] Okumura Y，Noda T，Eguchi H，et al. Hypoxia-Induced PLOD2 is a Key Regulator in Epithelial-Mesenchymal Transition and Chemoresistance in Biliary Tract Cancer [J]. Ann Surg Oncol，2018，25（12）：3728-3737.
[20] Wang D，Zhang S，Chen F. High Expression of PLOD1 Drives Tumorigenesis and Affects Clinical Outcome in Gastrointestinal Carcinoma [J]. Genet Test Mol Biomarkers，2018，22（6）：366-373.
[21] Tsai CK，Huang LC，Tsai WC，et al. Overexpression of PLOD3 promotes tumor progression and poor prognosis in gliomas [J]. Oncotarget，2018，9（21）：15 705-15 720.
[22] Noda T，Yamamoto H，Takemasa I，et al. PLOD2 induced under hypoxia is a novel prognostic factor for hepatocellular carcinoma after curative resection [J]. Liver Int，2012，32（1）：110-118.
[23] Elsemman IE，Mardinoglu A，Shoaie S，et al. Systems biology analysis of hepatitis C virus infection reveals the role of copy number increases in regions of chromosome 1q in hepatocellular carcinoma metabolism [J]. Mol Biosyst，2016，12（5）：1496-1506.
[24] Kiyozumi Y，Iwatsuki M，Kurashige J，et al. PLOD2 as a potential regulator of peritoneal dissemination in gastric cancer [J]. Int J Cancer，2018，143（5）：1202-1211.
[25] Wang B，Xu L，Ge Y，et al. PLOD3 is Upregulated in Gastric Cancer and Correlated with Clinicopathologic Characteristics [J]. Clin Lab，2019，65（1）.
[26] Verano-Braga T，Gorshkov V，Munthe S. SuperQuant-assisted comparative proteome analysis of glioblastoma subpopulations allows for identification of potential novel therapeutic targets and cell markers [J]. Oncotarget，2018，9（10）：9400-9414.