维甲酸经基因及非基因途径抗肿瘤治疗的研究进展
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摘要
维甲酸是维生素A的活性代谢物,在胚胎发育和多种肿瘤细胞的分化、增殖、凋亡及耐药方面发挥重要作用。维甲酸除可通过经典的基因途径(即通过与核受体家族成员结合调节下游靶基因表达)外,也可通过非基因途径(即核外和非转录效应)而发挥抗肿瘤效应。
Retinoic acid, an active metabolite of vitamin A, exerts multiple effects on regulating embryonic development and inducing differentiation, proliferation, apoptosis as well as resistance in various cancer cells. Apart from the classic genomic action(binding to the nuclear receptors to regulate the expression of its downstream target genes), retinoic acids also play important roles in anti-cancer effect through non-genomic pathways(via extranuclear and non-transcriptional effects).
Retinoic acid, an active metabolite of vitamin A, exerts multiple effects on regulating embryonic development and inducing differentiation, proliferation, apoptosis as well as resistance in various cancer cells. Apart from the classic genomic action(binding to the nuclear receptors to regulate the expression of its downstream target genes), retinoic acids also play important roles in anti-cancer effect through non-genomic pathways(via extranuclear and non-transcriptional effects).
引文
[1]Veldhoen M,Ferreira C.Influence of nutrient-derived metabolites on lymphocyte immunity[J].Nat Med,2015,21(7):709-718.
[2]Canete A,Cano E,Munoz-Chapuli R,et al.Role of vitamin A/retinoic acid in regulation of embryonic and adult hematopoiesis[J].Nutrients,2017,9(2):159-176.
[3]Cabezas-Wallscheid N,Buettner F,Sommerkamp P,et al.Vitamin A-retinoic acid signaling regulates hematopoietic stem cell dormancy[J].Cell,2017,169(5):807-823.
[4]Larange A,Cheroutre H.Retinoic acid and retinoic acid receptors as pleiotropic modulators of the immune system[J].Annu Rev Immunol,2016,34(1):369-394.
[5]de The H,Pandolfi PP,Chen Z.Acute promyelocytic leukemia:A paradigm for oncoprotein-targeted cure[J].Cancer Cell,2017,32(5):552-560.
[6]Bauer R,Udonta F,Wroblewski M,et al.Blockade of myeloid-derived suppressor cell expansion with all-trans retinoic acid increases the efficacy of anti-angiogenic therapy[J].Cancer Res,2018,78(12):3220-3232.
[7]Bhatia AK,Lee JW,Pinto HA,et al.Double-blind,randomized phase3 trial of low-dose 13-cis retinoic acid in the prevention of second primaries in head and neck cancer:Long-term follow-up of a trial of the Eastern Cooperative Oncology Group-ACRIN Cancer Research Group(C0590)[J].Cancer,2017,123(23):4653-4662.
[8]Kraus LF,Scheurmann N,Frenzel DF,et al.9-cis-Retinoic acid induces a distinct regulatory dendritic cell phenotype that modulates murine delayed-type allergy[J].Contact Dermatitis,2018,78(1):41-54.
[9]Gkikas D,Tsampoula M,Politis PK.Nuclear receptors in neural stem/progenitor cell homeostasis[J].Cell Mol Life Sci,2017,74(22):4097-4120.
[10]Dou M,Zhou X,Fan Z,et al.Clinical significance of retinoic acid receptor beta promoter methylation in prostate cancer:A Metaanalysis[J].Cell Physiol Biochem,2018,45(6):2497-2505.
[11]Kojetin DJ,Burris TP.REV-ERB and ROR nuclear receptors as drug targets[J].Nat Rev Drug Discov,2014,13(3):197-216.
[12]Chebaro Y,Sirigu S,Amal I,et al.Allosteric regulation in the ligand binding domain of retinoic acid receptorgamma[J].PLoS One,2017,12(1):e0171043.
[13]Samarut E,Amal I,Markov GV,et al.Evolution of nuclear retinoic acid receptor alpha(RARalpha)phosphorylation sites.Serine gain provides fine-tuned regulation[J].Mol Biol Evol,2011,28(7):2125-2137.
[14]Al Tanoury Z,Piskunov A,Rochette-Egly C.Vitamin A and retinoid signaling:genomic and nongenomic effects[J].J Lipid Res,2013,54(7):1761-1775.
[15]Gudas LJ,Wagner JA.Retinoids regulate stem cell differentiation[J].J Cell Physiol,2011,226(2):322-330.
[16]le Maire A,Alvarez S,Shankaranarayanan P,et al.Retinoid receptors and therapeutic applications of RAR/RXR modulators[J].Curr Top Med Chem,2012,12(6):505-527.
[17]Evans RM,Mangelsdorf DJ.Nuclear receptors,RXR,and the big bang[J].Cell,2014,157(1):255-266.
[18]Ying M,Zhang L,Zhou Q,et al.The E3 ubiquitin protein ligase MDM2 dictates all-trans retinoic acid-induced osteoblastic differentiation of osteosarcoma cells by modulating the degradation of RARalpha[J].Oncogene,2016,35(33):4358-4367.
[19]Nellessen CM,Janzen V,Mayer K,et al.Successful treatment of acute promyelocytic leukemia in pregnancy with single-agent all-trans retinoic acid[J].Arch Gynecol Obstet,2018,297(2):281-284.
[20]Fakhimahmadi A,Nazmi F,Rahmati M,et al.Nucleostemin silencing induces differentiation and potentiates all-trans-retinoic acid effects in human acute promyelocytic leukemia NB4 cells via autophagy[J].Leuk Res,2017,63(1):15-21.
[21]di Masi A,Leboffe L,De Marinis E,et al.Retinoic acid receptors:from molecular mechanisms to cancer therapy[J].Mol Aspects Med,2015,41(1):1-115.
[22]Persaud SD,Park SW,Ishigami-Yuasa M,et al.All trans-retinoic acid analogs promote cancer cell apoptosis through non-genomic Crabp1mediating ERK1/2 phosphorylation[J].Sci Rep,2016,6(1):22396.
[23]Zeng W,Zhang C,Cheng H,et al.Targeting to the non-genomic activity of retinoic acid receptor-gamma by acacetin in hepatocellular carcinoma[J].Sci Rep,2017,7(1):348.
[24]Rondina MT,Freitag M,Pluthero FG,et al.Non-genomic activities of retinoic acid receptor alpha control actin cytoskeletal events in human platelets[J].J Thromb Haemost,2016,14(5):1082-1094.
[25]Persaud SD,Lin YW,Wu CY,et al.Cellular retinoic acid binding protein I mediates rapid non-canonical activation of ERK1/2 by alltrans retinoic acid[J].Cell Signal,2013,25(1):19-25.
[26]Papa F,Sardaro N,Lippolis R,et al.Activation of protein phosphatase 2A is responsible for increased content and inactivation of respiratory chain complex i induced by all-trans retinoic acid in human keratinocytes[J].J Biol Regul Homeost Agents,2016,30(2):389-398.
[27]Chatterjee A,Chatterji U.All-trans retinoic acid ameliorates arsenic-induced oxidative stress and apoptosis in the rat uterus by modulating MAPK signaling proteins[J].J Cell Biochem,2017,118(11):3796-3809.
[28]Zanotto-Filho A,Cammarota M,Gelain DP,et al.Retinoic acid induces apoptosis by a non-classical mechanism of ERK1/2activation[J].Toxicol In Vitro,2008,22(5):1205-1212.
[29]Yang L,Luo C,Chen C,et al.All-trans retinoic acid protects against doxorubicin-induced cardiotoxicity by activating the ERK2 signalling pathway[J].Br J Pharmacol,2016,173(2):357-371.
[30]Maurus K,Hufnagel A,Geiger F,et al.The AP-1 transcription factor FOSL1 causes melanocyte reprogramming and transformation[J].Oncogene,2017,36(36):5110-5121.
[31]Pasquali D,Chieffi P,Deery WJ,et al.Differential effects of alltrans-retinoic acid(RA)on Erk1/2 phosphorylation and cAMPaccumulation in normal and malignant human prostate epithelial cells:Erk1/2 inhibition restores RA-induced decrease of cell growth in malignant prostate cells[J].Eur J Endocrinol,2005,152(4):663-669.
[32]Ashton A,Stoney PN,Ransom J,et al.Rhythmic diurnal synthesis and signaling of retinoic acid in the rat pineal gland and its action to rapidly downregulate ERK phosphorylation[J].Mol Neurobiol,2018,55(11):8219-8235.
[33]Bruck N,Vitoux D,Ferry C,et al.A coordinated phosphorylation cascade initiated by p38MAPK/MSK1 directs RARalpha to target promoters[J].EMBO J,2009,28(1):34-47.
[34]Gianni M,Parrella E,Raska I Jr,et al.P38MAPK-dependent phosphorylation and degradation of SRC-3/AIB1 and RARalphamediated transcription[J].EMBO J,2006,25(4):739-751.
[35]Feyder M,Sodersten E,Santini E,et al.A role for mitogen-and stress-activated kinase 1 in L-DOPA-induced dyskinesia and FosBexpression[J].Biol Psychiatry,2016,79(5):362-371.
[36]Tochiki KK,Maiaru M,Norris C,et al.The mitogen and stressactivated protein kinase 1 regulates the rapid epigenetic tagging of dorsal horn neurons and nocifensive behaviour[J].Pain,2016,157(11):2594-2604.
[37]Rochette-Egly C.Retinoic acid signaling and mouse embryonic stem cell differentiation:Cross talk between genomic and non-genomic effects of RA[J].Biochim Biophys Acta,2015,1851(1):66-75.
[38]Grisouard J,Mayer D.Specific involvement of glycogen synthase kinase-3 in the function and activity of sex steroid hormone receptors reveals the complexity of their regulation[J].J Steroid Biochem Mol Biol,2009,117(4/5):87-92.
[39]Jung YS,Cheong HJ,Kim SJ,et al.Src family kinase inhibitor PP2enhances differentiation of acute promyelocytic leukemia cell line induced by combination of all-trans-retinoic acid and arsenic trioxide[J].Leuk Res,2014,38(8):977-982.
[40]Wszelaki N,Melzig MF.Research on an in vitro cell system for testing the neurotoxicity of kynurenine pathway metabolites[J].Pharmazie,2011,66(11):899-903.
[41]Congleton J,Shen M,MacDonald R,et al.Phosphorylation of c-Cbl and p85 PI3K driven by all-trans retinoic acid and CD38 depends on Lyn kinase activity[J].Cell Signal,2014,26(7):1589-1597.
[42]Iskakova M,Karbyshev M,Piskunov A,et al.Nuclear and extranuclear effects of vitamin A[J].Can J Physiol Pharmacol,2015,93(12):1065-1075.
[43]de Hoog E,Lukewich MK,Spencer GE.Retinoic acid inhibits neuronal voltage-gated calcium channels[J].Cell Calcium,2018,72(1):51-61.
[44]Chen N,Napoli JL.All-trans-retinoic acid stimulates translation and induces spine formation in hippocampal neurons through a membrane-associated RARalpha[J].FASEB J,2008,22(1):236-245.
[45]Kelleher RJ 3rd,Govindarajan A,Jung HY,et al.Translational control by MAPK signaling in long-term synaptic plasticity and memory[J].Cell,2004,116(3):467-479.
[46]Glanz S,Mirsaidi A,Lopez-Fagundo C,et al.Loss-of-function of HtrA1 abrogates all-trans retinoic acid-induced osteogenic differentiation of mouse adipose-derived stromal cells through deficiencies in p70S6K activation[J].Stem Cells Dev,2016,25(9):687-698.
[47]Piskunov A,Rochette-Egly C.A retinoic acid receptor RARalpha pool present in membrane lipid rafts forms complexes with G protein alphaQ to activate p38MAPK[J].Oncogene,2012,31(28):3333-3345.
[48]Han YH,Zhou H,Kim JH,et al.A unique cytoplasmic localization of retinoic acid receptor-gamma and its regulations[J].J Biol Chem,2009,284(27):18503-18514.
[49]Santos NC,Kim KH.Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to folliclestimulating hormone signaling[J].Endocrinology,2010,151(5):2361-2372.
[50]Zhu L,Santos NC,Kim KH.Small ubiquitin-like modifier-2modification of retinoic acid receptor-alpha regulates its subcellular localization and transcriptional activity[J].Endocrinology,2009,150(12):5586-5595.
[51]Ahner A,Gong X,Frizzell RA.Divergent signaling via SUMOmodification:potential for CFTR modulation[J].Am J Physiol Cell Physiol,2016,310(3):C175-180.
[52]Mezaki Y,Yamaguchi N,Yoshikawa K,et al.Insoluble,speckled cytosolic distribution of retinoic acid receptor alpha protein as a marker of hepatic stellate cell activation in vitro[J].J Histochem Cytochem,2009,57(7):687-699.
[53]Park UH,Kim EJ,Um SJ.A novel cytoplasmic adaptor for retinoic acid receptor(RAR)and thyroid receptor functions as a Derepressor of RAR in the absence of retinoic acid[J].J Biol Chem,2010,285(44):34269-34278.
[54]Zhao KN,Masci PP,Chen J,et al.Calcium prevents retinoic acid-induced disruption of the spectrin-based cytoskeleton in keratinocytes through the Src/PI3K-p85alpha/AKT/PKCdelta/beta-adducin pathways[J].Cell Calcium,2013,54(3):151-162.
[55]Neels JG,Grimaldi PA.Physiological functions of peroxisome proliferator-activated receptor beta[J].Physiol Rev,2014,94(3):795-858.
[56]Schug TT,Berry DC,Shaw NS,et al.Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors[J].Cell,2007,129(4):723-733.
[57]Peters JM,Shah YM,Gonzalez FJ.The role of perox isome p r o l i f e r a t o r-a c t i v a t e d r e c e p t o r s i n c a r c i n o g e n e s i s a n d chemoprevention[J].Nat Rev Cancer,2012,12(3):181-195.
[58]Feng S,Xu S,Wen Z,et al.Retinoic acid-related orphan receptor RORbeta,circadian rhythm abnormalities and tumorigenesis(Review)[J].Int J Mol Med,2015,35(6):1493-1500.
[59]Berry DC,O'Byrne SM,Vreeland AC,et al.Cross talk between signaling and vitamin A transport by the retinol-binding protein receptor STRA6[J].Mol Cell Biol,2012,32(15):3164-3175.
[60]Yang H,Ma P,Cao Y,et al.ECPIRM,a potential therapeutic agent for cutaneous T-cell lymphoma,inhibits cell proliferation and promotes apoptosis via a JAK/STAT pathway the biological effect of ECPIRMin CTCL cell[J].Anticancer Agents Med Chem,2018,18(3):401-411.
[61]Maude SL,Dolai S,Delgado-Martin C,et al.Efficacy of JAK/STAT pathway inhibition in murine xenograft models of early T-cell precursor(ETP)acute lymphoblastic leukemia[J].Blood,2015,125(11):1759-1767.
[62]Vainchenker W,Constantinescu SN.JAK/STAT signaling in hematological malignancies[J].Oncogene,2013,32(21):2601-2613.
[63]Balmer JE,BlomhoffR.Gene expression regulation by retinoic acid[J].J Lipid Res,2002,43(11):1773-1808.
[2]Canete A,Cano E,Munoz-Chapuli R,et al.Role of vitamin A/retinoic acid in regulation of embryonic and adult hematopoiesis[J].Nutrients,2017,9(2):159-176.
[3]Cabezas-Wallscheid N,Buettner F,Sommerkamp P,et al.Vitamin A-retinoic acid signaling regulates hematopoietic stem cell dormancy[J].Cell,2017,169(5):807-823.
[4]Larange A,Cheroutre H.Retinoic acid and retinoic acid receptors as pleiotropic modulators of the immune system[J].Annu Rev Immunol,2016,34(1):369-394.
[5]de The H,Pandolfi PP,Chen Z.Acute promyelocytic leukemia:A paradigm for oncoprotein-targeted cure[J].Cancer Cell,2017,32(5):552-560.
[6]Bauer R,Udonta F,Wroblewski M,et al.Blockade of myeloid-derived suppressor cell expansion with all-trans retinoic acid increases the efficacy of anti-angiogenic therapy[J].Cancer Res,2018,78(12):3220-3232.
[7]Bhatia AK,Lee JW,Pinto HA,et al.Double-blind,randomized phase3 trial of low-dose 13-cis retinoic acid in the prevention of second primaries in head and neck cancer:Long-term follow-up of a trial of the Eastern Cooperative Oncology Group-ACRIN Cancer Research Group(C0590)[J].Cancer,2017,123(23):4653-4662.
[8]Kraus LF,Scheurmann N,Frenzel DF,et al.9-cis-Retinoic acid induces a distinct regulatory dendritic cell phenotype that modulates murine delayed-type allergy[J].Contact Dermatitis,2018,78(1):41-54.
[9]Gkikas D,Tsampoula M,Politis PK.Nuclear receptors in neural stem/progenitor cell homeostasis[J].Cell Mol Life Sci,2017,74(22):4097-4120.
[10]Dou M,Zhou X,Fan Z,et al.Clinical significance of retinoic acid receptor beta promoter methylation in prostate cancer:A Metaanalysis[J].Cell Physiol Biochem,2018,45(6):2497-2505.
[11]Kojetin DJ,Burris TP.REV-ERB and ROR nuclear receptors as drug targets[J].Nat Rev Drug Discov,2014,13(3):197-216.
[12]Chebaro Y,Sirigu S,Amal I,et al.Allosteric regulation in the ligand binding domain of retinoic acid receptorgamma[J].PLoS One,2017,12(1):e0171043.
[13]Samarut E,Amal I,Markov GV,et al.Evolution of nuclear retinoic acid receptor alpha(RARalpha)phosphorylation sites.Serine gain provides fine-tuned regulation[J].Mol Biol Evol,2011,28(7):2125-2137.
[14]Al Tanoury Z,Piskunov A,Rochette-Egly C.Vitamin A and retinoid signaling:genomic and nongenomic effects[J].J Lipid Res,2013,54(7):1761-1775.
[15]Gudas LJ,Wagner JA.Retinoids regulate stem cell differentiation[J].J Cell Physiol,2011,226(2):322-330.
[16]le Maire A,Alvarez S,Shankaranarayanan P,et al.Retinoid receptors and therapeutic applications of RAR/RXR modulators[J].Curr Top Med Chem,2012,12(6):505-527.
[17]Evans RM,Mangelsdorf DJ.Nuclear receptors,RXR,and the big bang[J].Cell,2014,157(1):255-266.
[18]Ying M,Zhang L,Zhou Q,et al.The E3 ubiquitin protein ligase MDM2 dictates all-trans retinoic acid-induced osteoblastic differentiation of osteosarcoma cells by modulating the degradation of RARalpha[J].Oncogene,2016,35(33):4358-4367.
[19]Nellessen CM,Janzen V,Mayer K,et al.Successful treatment of acute promyelocytic leukemia in pregnancy with single-agent all-trans retinoic acid[J].Arch Gynecol Obstet,2018,297(2):281-284.
[20]Fakhimahmadi A,Nazmi F,Rahmati M,et al.Nucleostemin silencing induces differentiation and potentiates all-trans-retinoic acid effects in human acute promyelocytic leukemia NB4 cells via autophagy[J].Leuk Res,2017,63(1):15-21.
[21]di Masi A,Leboffe L,De Marinis E,et al.Retinoic acid receptors:from molecular mechanisms to cancer therapy[J].Mol Aspects Med,2015,41(1):1-115.
[22]Persaud SD,Park SW,Ishigami-Yuasa M,et al.All trans-retinoic acid analogs promote cancer cell apoptosis through non-genomic Crabp1mediating ERK1/2 phosphorylation[J].Sci Rep,2016,6(1):22396.
[23]Zeng W,Zhang C,Cheng H,et al.Targeting to the non-genomic activity of retinoic acid receptor-gamma by acacetin in hepatocellular carcinoma[J].Sci Rep,2017,7(1):348.
[24]Rondina MT,Freitag M,Pluthero FG,et al.Non-genomic activities of retinoic acid receptor alpha control actin cytoskeletal events in human platelets[J].J Thromb Haemost,2016,14(5):1082-1094.
[25]Persaud SD,Lin YW,Wu CY,et al.Cellular retinoic acid binding protein I mediates rapid non-canonical activation of ERK1/2 by alltrans retinoic acid[J].Cell Signal,2013,25(1):19-25.
[26]Papa F,Sardaro N,Lippolis R,et al.Activation of protein phosphatase 2A is responsible for increased content and inactivation of respiratory chain complex i induced by all-trans retinoic acid in human keratinocytes[J].J Biol Regul Homeost Agents,2016,30(2):389-398.
[27]Chatterjee A,Chatterji U.All-trans retinoic acid ameliorates arsenic-induced oxidative stress and apoptosis in the rat uterus by modulating MAPK signaling proteins[J].J Cell Biochem,2017,118(11):3796-3809.
[28]Zanotto-Filho A,Cammarota M,Gelain DP,et al.Retinoic acid induces apoptosis by a non-classical mechanism of ERK1/2activation[J].Toxicol In Vitro,2008,22(5):1205-1212.
[29]Yang L,Luo C,Chen C,et al.All-trans retinoic acid protects against doxorubicin-induced cardiotoxicity by activating the ERK2 signalling pathway[J].Br J Pharmacol,2016,173(2):357-371.
[30]Maurus K,Hufnagel A,Geiger F,et al.The AP-1 transcription factor FOSL1 causes melanocyte reprogramming and transformation[J].Oncogene,2017,36(36):5110-5121.
[31]Pasquali D,Chieffi P,Deery WJ,et al.Differential effects of alltrans-retinoic acid(RA)on Erk1/2 phosphorylation and cAMPaccumulation in normal and malignant human prostate epithelial cells:Erk1/2 inhibition restores RA-induced decrease of cell growth in malignant prostate cells[J].Eur J Endocrinol,2005,152(4):663-669.
[32]Ashton A,Stoney PN,Ransom J,et al.Rhythmic diurnal synthesis and signaling of retinoic acid in the rat pineal gland and its action to rapidly downregulate ERK phosphorylation[J].Mol Neurobiol,2018,55(11):8219-8235.
[33]Bruck N,Vitoux D,Ferry C,et al.A coordinated phosphorylation cascade initiated by p38MAPK/MSK1 directs RARalpha to target promoters[J].EMBO J,2009,28(1):34-47.
[34]Gianni M,Parrella E,Raska I Jr,et al.P38MAPK-dependent phosphorylation and degradation of SRC-3/AIB1 and RARalphamediated transcription[J].EMBO J,2006,25(4):739-751.
[35]Feyder M,Sodersten E,Santini E,et al.A role for mitogen-and stress-activated kinase 1 in L-DOPA-induced dyskinesia and FosBexpression[J].Biol Psychiatry,2016,79(5):362-371.
[36]Tochiki KK,Maiaru M,Norris C,et al.The mitogen and stressactivated protein kinase 1 regulates the rapid epigenetic tagging of dorsal horn neurons and nocifensive behaviour[J].Pain,2016,157(11):2594-2604.
[37]Rochette-Egly C.Retinoic acid signaling and mouse embryonic stem cell differentiation:Cross talk between genomic and non-genomic effects of RA[J].Biochim Biophys Acta,2015,1851(1):66-75.
[38]Grisouard J,Mayer D.Specific involvement of glycogen synthase kinase-3 in the function and activity of sex steroid hormone receptors reveals the complexity of their regulation[J].J Steroid Biochem Mol Biol,2009,117(4/5):87-92.
[39]Jung YS,Cheong HJ,Kim SJ,et al.Src family kinase inhibitor PP2enhances differentiation of acute promyelocytic leukemia cell line induced by combination of all-trans-retinoic acid and arsenic trioxide[J].Leuk Res,2014,38(8):977-982.
[40]Wszelaki N,Melzig MF.Research on an in vitro cell system for testing the neurotoxicity of kynurenine pathway metabolites[J].Pharmazie,2011,66(11):899-903.
[41]Congleton J,Shen M,MacDonald R,et al.Phosphorylation of c-Cbl and p85 PI3K driven by all-trans retinoic acid and CD38 depends on Lyn kinase activity[J].Cell Signal,2014,26(7):1589-1597.
[42]Iskakova M,Karbyshev M,Piskunov A,et al.Nuclear and extranuclear effects of vitamin A[J].Can J Physiol Pharmacol,2015,93(12):1065-1075.
[43]de Hoog E,Lukewich MK,Spencer GE.Retinoic acid inhibits neuronal voltage-gated calcium channels[J].Cell Calcium,2018,72(1):51-61.
[44]Chen N,Napoli JL.All-trans-retinoic acid stimulates translation and induces spine formation in hippocampal neurons through a membrane-associated RARalpha[J].FASEB J,2008,22(1):236-245.
[45]Kelleher RJ 3rd,Govindarajan A,Jung HY,et al.Translational control by MAPK signaling in long-term synaptic plasticity and memory[J].Cell,2004,116(3):467-479.
[46]Glanz S,Mirsaidi A,Lopez-Fagundo C,et al.Loss-of-function of HtrA1 abrogates all-trans retinoic acid-induced osteogenic differentiation of mouse adipose-derived stromal cells through deficiencies in p70S6K activation[J].Stem Cells Dev,2016,25(9):687-698.
[47]Piskunov A,Rochette-Egly C.A retinoic acid receptor RARalpha pool present in membrane lipid rafts forms complexes with G protein alphaQ to activate p38MAPK[J].Oncogene,2012,31(28):3333-3345.
[48]Han YH,Zhou H,Kim JH,et al.A unique cytoplasmic localization of retinoic acid receptor-gamma and its regulations[J].J Biol Chem,2009,284(27):18503-18514.
[49]Santos NC,Kim KH.Activity of retinoic acid receptor-alpha is directly regulated at its protein kinase A sites in response to folliclestimulating hormone signaling[J].Endocrinology,2010,151(5):2361-2372.
[50]Zhu L,Santos NC,Kim KH.Small ubiquitin-like modifier-2modification of retinoic acid receptor-alpha regulates its subcellular localization and transcriptional activity[J].Endocrinology,2009,150(12):5586-5595.
[51]Ahner A,Gong X,Frizzell RA.Divergent signaling via SUMOmodification:potential for CFTR modulation[J].Am J Physiol Cell Physiol,2016,310(3):C175-180.
[52]Mezaki Y,Yamaguchi N,Yoshikawa K,et al.Insoluble,speckled cytosolic distribution of retinoic acid receptor alpha protein as a marker of hepatic stellate cell activation in vitro[J].J Histochem Cytochem,2009,57(7):687-699.
[53]Park UH,Kim EJ,Um SJ.A novel cytoplasmic adaptor for retinoic acid receptor(RAR)and thyroid receptor functions as a Derepressor of RAR in the absence of retinoic acid[J].J Biol Chem,2010,285(44):34269-34278.
[54]Zhao KN,Masci PP,Chen J,et al.Calcium prevents retinoic acid-induced disruption of the spectrin-based cytoskeleton in keratinocytes through the Src/PI3K-p85alpha/AKT/PKCdelta/beta-adducin pathways[J].Cell Calcium,2013,54(3):151-162.
[55]Neels JG,Grimaldi PA.Physiological functions of peroxisome proliferator-activated receptor beta[J].Physiol Rev,2014,94(3):795-858.
[56]Schug TT,Berry DC,Shaw NS,et al.Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors[J].Cell,2007,129(4):723-733.
[57]Peters JM,Shah YM,Gonzalez FJ.The role of perox isome p r o l i f e r a t o r-a c t i v a t e d r e c e p t o r s i n c a r c i n o g e n e s i s a n d chemoprevention[J].Nat Rev Cancer,2012,12(3):181-195.
[58]Feng S,Xu S,Wen Z,et al.Retinoic acid-related orphan receptor RORbeta,circadian rhythm abnormalities and tumorigenesis(Review)[J].Int J Mol Med,2015,35(6):1493-1500.
[59]Berry DC,O'Byrne SM,Vreeland AC,et al.Cross talk between signaling and vitamin A transport by the retinol-binding protein receptor STRA6[J].Mol Cell Biol,2012,32(15):3164-3175.
[60]Yang H,Ma P,Cao Y,et al.ECPIRM,a potential therapeutic agent for cutaneous T-cell lymphoma,inhibits cell proliferation and promotes apoptosis via a JAK/STAT pathway the biological effect of ECPIRMin CTCL cell[J].Anticancer Agents Med Chem,2018,18(3):401-411.
[61]Maude SL,Dolai S,Delgado-Martin C,et al.Efficacy of JAK/STAT pathway inhibition in murine xenograft models of early T-cell precursor(ETP)acute lymphoblastic leukemia[J].Blood,2015,125(11):1759-1767.
[62]Vainchenker W,Constantinescu SN.JAK/STAT signaling in hematological malignancies[J].Oncogene,2013,32(21):2601-2613.
[63]Balmer JE,BlomhoffR.Gene expression regulation by retinoic acid[J].J Lipid Res,2002,43(11):1773-1808.