FABP4与肿瘤上皮-间质转化信号通路相关性的研究进展
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摘要
近年来,脂肪酸结合蛋白家族4(FABP4)在肿瘤转移中的研究机制广受关注。FABPs是一种广泛存在于哺乳动物脂肪、肝脏、小肠等多种器官组织细胞内的小分子胞内蛋白,脂肪酸结合蛋白的脂肪细胞型称为FABP4。与细胞膜上其他因子相比,FABP4可以优先与脂肪酸结合,进入胞质进行氧化、酯化等化学修饰,转运脂肪酸至身体各个部位,参与脂质合成、代谢及肿瘤转移的信号转导。肿瘤转移即肿瘤细胞丢失自身特性,不断增殖生长,上皮-间质转化是启动恶性肿瘤侵袭与转移的关键步骤。
In recent years,the mechanism of fatty acid binding proteins( FABP) 4 in cancer metastasis has attracted much attention. FABPs is a kind of small intracellular proteins widely existing in mammalian fat,liver,small intestine and other cells,and the adipocyte fatty acid binding type is called FABP4. Studies have shown that compared with other factors on the cell membrane,FABP4 can preferentially bind to fatty acids,enter the cytoplasm for chemical modification such as oxidation and esterification,transport fatty acids to various parts of the body,and participate in the signal transduction of lipid synthesis,metabolism and tumor metastasis. Metastasis of cancer means that carcinoma cells lose their own characteristics and proliferate continuously. Epithelial-mesenchymal transition is the key step to initiate the invasion and metastasis of malignant tumors.
In recent years,the mechanism of fatty acid binding proteins( FABP) 4 in cancer metastasis has attracted much attention. FABPs is a kind of small intracellular proteins widely existing in mammalian fat,liver,small intestine and other cells,and the adipocyte fatty acid binding type is called FABP4. Studies have shown that compared with other factors on the cell membrane,FABP4 can preferentially bind to fatty acids,enter the cytoplasm for chemical modification such as oxidation and esterification,transport fatty acids to various parts of the body,and participate in the signal transduction of lipid synthesis,metabolism and tumor metastasis. Metastasis of cancer means that carcinoma cells lose their own characteristics and proliferate continuously. Epithelial-mesenchymal transition is the key step to initiate the invasion and metastasis of malignant tumors.
引文
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[19]张挚,吴江,梁冰,等.缺氧诱导因子-1α与乳腺浸润性导管癌上皮-间质转化的关系[J].山东医药,2012,52(3):90-92.
[20]张育军,陈海珍,赵春丽,等.BCAR3诱导乳腺癌上皮间质转化及与癌细胞迁移、侵袭的关系[J].武汉大学学报(医学版),2010,31(4):471-475.
[21]智仁厚,刘建生,郑刚.Twist和E-cadherin在胰腺癌中的表达和意义[J].中国医疗前沿,2011,6(2):14-15.
[22]Zeng C,Xing R,Liu J,et al.Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis[J].Apoptosis,2016,21(1):1-12.
[23]Harjes U,Bridges E,Mcintyre A,et al.Fatty acid-binding protein 4,a point of convergence for angiogenic and metabolic signaling pathways in endothelial cells[J].J Biol Chem,2014,289(33):23168-23176.
[24]李梅.血清A-FABP及HIF-1α测定在新生儿缺氧缺血性脑损伤发病中的临床意义[D].石家庄:河北医科大学,2010.
[25]Su BH,Qu J,Song M,et al.NOTCH1 signaling contributes to cell growth,anti-apoptosis and metastasis in salivary adenoid cystic carcinoma[J].Oncotarget,2014,5(16):6885-6895.
[26]Xu J,Yun X,Jiang J,et al.Hepatitis B virus X protein blunts senescence-like growth arrest of human hepatocellular carcinoma by reducing Notch1 cleavage[J].Hepatology,2010,52(1):142-154.
[27]Wang Z,Zhang Y,Banerjee S,et al.Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells[J].Cancer,2006,106(11):2503-2513.
[28]Girona J,Rosales R,Plana N,et al.FABP4 induces vascular smooth muscle cell proliferation and migration through a MAPK-dependent pathway[J].PLo S One,2013,8(11):e81914.
[29]Prasad SB,Yadav SS,Das M,et al.PI3K/AKT pathway-mediated regulation of p27(Kip1)is associated with cell cycle arrest and apoptosis in cervical cancer[J].Cell Oncol(Dordr),2015,38(3):215-225.
[30]李学凤.FABP5/PPARβ/δ信号转导通路对Ras雄性小鼠肝癌发生发展的影响[D].大连:大连医科大学,2016.
[31]Jin J,Zhang Z,Zhang S,et al.Fatty acid binding protein 4 promotes epithelial-mesenchymal transition in cervical squamous cell carcinoma through AKT/GSK3beta/Snail signaling pathway[J].Mol Cell Endocrinol,2018,461:155-164.
[32]Vincent T,Neve EP,Johnson JR,et al.A SNAIL1-SMAD3/4transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition[J].Nat Cell Biol,2009,11(8):943-950.
[33]徐然,赵俊刚,石文君.RGC32与转化生长因子β1在肺腺癌细胞增殖过程中调控关系的研究[J].现代肿瘤医学,2014,22(5):1009-1011.
[34]毛华,黄纯炽,赵敏芳,等.p38MAPK信号传导通路调控VEGF诱导肝癌细胞黏附作用[J].世界华人消化杂志,2006,14(8):778-783.
[35]卢韵碧,刘志娴,魏尔清.上皮-间质转化在肿瘤发生发展中的作用研究进展[J].浙江大学学报(医学版),2015,44(2):211-216.
[36]谈笑.FABP4对3T3-L1脂肪细胞中脂肪酸代谢和线粒体功能的影响[D].杨凌:西北农林科技大学,2014.
[37]Tan NS,Shaw NS,Vinckenbosch N,et al.Selective cooperation between fatty acid binding proteins and peroxisome proliferatoractivated receptors in regulating transcription[J].Mol Cell Biol,2002,22(14):5114-5127.
[38]王琨.脂肪型脂肪酸结合蛋白通过内质网应激诱导系膜细胞凋亡的分子机制[D].石家庄:河北医科大学,2016.
[39]陈永熙,王伟铭,周同,等.PPAR-γ作用及其相关信号转导途径[J].细胞生物学杂志,2006,28(3):382-386.
[2]Cabia B,Andrade S,Carreira MC,et al.A role for novel adipose tissue-secreted factors in obesity-related carcinogenesis[J].Obes Rev,2016,17(4):361-376.
[3]周兰,赵玉华,王晓东,等.FASN和A-FABP在乳腺浸润性导管癌中的表达及其与临床病理学特征的关系[J].四川大学学报(医学版),2015,46(2):228-233.
[4]Nieman KM,Kenny HA,Penicka CV,et al.Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth[J].Nat Med,2011,17(11):1498-1503.
[5]Guaita-Esteruelas S,Saavedra-Garcia P,Bosquet A,et al.Adipose-Derived Fatty Acid-Binding Proteins Plasma Concentrations Are Increased in Breast Cancer Patients[J].Oncologist,2017,22(11):1309-1315.
[6]Uehara H,Takahashi T,Oha M,et al.Exogenous fatty acid binding protein 4 promotes human prostate cancer cell progression[J].Int JCancer,2014,135(11):2558-2568.
[7]Nie J,Zhang J,Wang L,et al.Adipocytes promote cholangiocarcinoma metastasis through fatty acid binding protein 4[J].J Exp Clin Cancer Res,2017,36(1):183.
[8]杨莉丽,于雪梅.脂肪细胞型脂肪酸结合蛋白与2型糖尿病的关系[J].国际内分泌代谢杂志,2013,33(2):122-125.
[9]Floresta G,Pistara V,Amata E,et al.Adipocyte fatty acid binding protein 4(FABP4)inhibitors.A comprehensive systematic review[J].Eur J Med Chem,2017,138:854-873.
[10]Gillilan RE,Ayers SD,Noy N.Structural basis for activation of fatty acid-binding protein 4[J].J Mol Biol,2007,372(5):1246-1260.
[11]Furuhashi M,Saitoh S,Shimamoto K,et al.Fatty Acid-Binding Protein 4(FABP4):Pathophysiological Insights and Potent Clinical Biomarker of Metabolic and Cardiovascular Diseases[J].Clin Med Insights Cardiol,2014,8(Suppl 3):23-33.
[12]杨茜,邹大进.脂肪细胞型脂肪酸结合蛋白与胆固醇代谢[J].中华内分泌代谢杂志,2015,31(7):625-628.
[13]Elmasri H,Karaaslan C,Teper Y,et al.Fatty acid binding protein4 is a target of VEGF and a regulator of cell proliferation in endothelial cells[J].FASEB J,2009,23(11):3865-3873.
[14]Elmasri H,Ghelfi E,Yu CW,et al.Endothelial cell-fatty acid binding protein 4 promotes angiogenesis:Role of stem cell factor/c-kit pathway[J].Angiogenesis,2012,15(3):457-468.
[15]Tang Z,Shen Q,Xie H,et al.Elevated expression of FABP3 and FABP4 cooperatively correlates with poor prognosis in non-small cell lung cancer(NSCLC)[J].Oncotarget,2016,7(29):46253-46262.
[16]Guaita-Esteruelas S,Bosquet A,Saavedra P,et al.Exogenous FABP4 increases breast cancer cell proliferation and activates the expression of fatty acid transport proteins[J].Mol Carcinog,2017,56(1):208-217.
[17]李蒙,吴玖斌,张培彤.E-钙黏蛋白、N-钙黏蛋白及波形蛋白在肿瘤转移中应用的研究进展[J].肿瘤研究与临床,2016,28(2):132-136.
[18]Han Z,Jing Y,Xia Y,et al.Mesenchymal stem cells contribute to the chemoresistance of hepatocellular carcinoma cells in inflammatory environment by inducing autophagy[J].Cell Biosci,2014,4:22.
[19]张挚,吴江,梁冰,等.缺氧诱导因子-1α与乳腺浸润性导管癌上皮-间质转化的关系[J].山东医药,2012,52(3):90-92.
[20]张育军,陈海珍,赵春丽,等.BCAR3诱导乳腺癌上皮间质转化及与癌细胞迁移、侵袭的关系[J].武汉大学学报(医学版),2010,31(4):471-475.
[21]智仁厚,刘建生,郑刚.Twist和E-cadherin在胰腺癌中的表达和意义[J].中国医疗前沿,2011,6(2):14-15.
[22]Zeng C,Xing R,Liu J,et al.Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis[J].Apoptosis,2016,21(1):1-12.
[23]Harjes U,Bridges E,Mcintyre A,et al.Fatty acid-binding protein 4,a point of convergence for angiogenic and metabolic signaling pathways in endothelial cells[J].J Biol Chem,2014,289(33):23168-23176.
[24]李梅.血清A-FABP及HIF-1α测定在新生儿缺氧缺血性脑损伤发病中的临床意义[D].石家庄:河北医科大学,2010.
[25]Su BH,Qu J,Song M,et al.NOTCH1 signaling contributes to cell growth,anti-apoptosis and metastasis in salivary adenoid cystic carcinoma[J].Oncotarget,2014,5(16):6885-6895.
[26]Xu J,Yun X,Jiang J,et al.Hepatitis B virus X protein blunts senescence-like growth arrest of human hepatocellular carcinoma by reducing Notch1 cleavage[J].Hepatology,2010,52(1):142-154.
[27]Wang Z,Zhang Y,Banerjee S,et al.Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells[J].Cancer,2006,106(11):2503-2513.
[28]Girona J,Rosales R,Plana N,et al.FABP4 induces vascular smooth muscle cell proliferation and migration through a MAPK-dependent pathway[J].PLo S One,2013,8(11):e81914.
[29]Prasad SB,Yadav SS,Das M,et al.PI3K/AKT pathway-mediated regulation of p27(Kip1)is associated with cell cycle arrest and apoptosis in cervical cancer[J].Cell Oncol(Dordr),2015,38(3):215-225.
[30]李学凤.FABP5/PPARβ/δ信号转导通路对Ras雄性小鼠肝癌发生发展的影响[D].大连:大连医科大学,2016.
[31]Jin J,Zhang Z,Zhang S,et al.Fatty acid binding protein 4 promotes epithelial-mesenchymal transition in cervical squamous cell carcinoma through AKT/GSK3beta/Snail signaling pathway[J].Mol Cell Endocrinol,2018,461:155-164.
[32]Vincent T,Neve EP,Johnson JR,et al.A SNAIL1-SMAD3/4transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition[J].Nat Cell Biol,2009,11(8):943-950.
[33]徐然,赵俊刚,石文君.RGC32与转化生长因子β1在肺腺癌细胞增殖过程中调控关系的研究[J].现代肿瘤医学,2014,22(5):1009-1011.
[34]毛华,黄纯炽,赵敏芳,等.p38MAPK信号传导通路调控VEGF诱导肝癌细胞黏附作用[J].世界华人消化杂志,2006,14(8):778-783.
[35]卢韵碧,刘志娴,魏尔清.上皮-间质转化在肿瘤发生发展中的作用研究进展[J].浙江大学学报(医学版),2015,44(2):211-216.
[36]谈笑.FABP4对3T3-L1脂肪细胞中脂肪酸代谢和线粒体功能的影响[D].杨凌:西北农林科技大学,2014.
[37]Tan NS,Shaw NS,Vinckenbosch N,et al.Selective cooperation between fatty acid binding proteins and peroxisome proliferatoractivated receptors in regulating transcription[J].Mol Cell Biol,2002,22(14):5114-5127.
[38]王琨.脂肪型脂肪酸结合蛋白通过内质网应激诱导系膜细胞凋亡的分子机制[D].石家庄:河北医科大学,2016.
[39]陈永熙,王伟铭,周同,等.PPAR-γ作用及其相关信号转导途径[J].细胞生物学杂志,2006,28(3):382-386.