Caveolin-1在肿瘤中的作用机制的研究进展
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摘要
小窝蛋白-1(Caveolin-1)是caveolae上的主要结构功能蛋白,通过它的脚手架区(CSD)与多个重要蛋白直接结合,形成信号通路的枢纽中心,在细胞增殖、迁移和分化,肿瘤的发生和转移等生理、病理过程中发挥重要作用。在正常生理条件下和结肠癌、肝癌、乳腺癌等肿瘤的早期,Caveolin-1-信号分子复合物负性调控各种信号通路。而在泌尿系肿瘤的各个时期和其他大多数肿瘤的晚期,Caveolin-1异常表达,激活各种生长信号的传导,促进肿瘤细胞生长、增殖和转移。Caveolin-1在肿瘤中表现出的双重效应与它调控的信号通路相关。本文将就Caveolin-1在肿瘤细胞中调控的信号通路做具体阐述。
Caveolin-1 is the main structural and functional protein in the caveolae.A variety of important signal proteins combined with the scaffold area(CSD),forming the center of signalings and regulating.In cell proliferation,migration and differentiation,tumorigenesis and metastasis and other physiological,pathological processes play an important role.In normal physiological conditions and the early of colon cancer,liver cancer,breast cancer,Caveolin-1 inhibit these signalings proteins,whlie in each period of urinary tract tumors and the late of others tumors,the overexpression of Caveolin–1 promotes all sorts of growth signals and induces tumor cells growth,proliferation and metastasis.The double effect of Caveolin-1 in tumor is related to its signalings.This review will elaborate signalings regulated by Caveolin–1 in tumor cells.
Caveolin-1 is the main structural and functional protein in the caveolae.A variety of important signal proteins combined with the scaffold area(CSD),forming the center of signalings and regulating.In cell proliferation,migration and differentiation,tumorigenesis and metastasis and other physiological,pathological processes play an important role.In normal physiological conditions and the early of colon cancer,liver cancer,breast cancer,Caveolin-1 inhibit these signalings proteins,whlie in each period of urinary tract tumors and the late of others tumors,the overexpression of Caveolin–1 promotes all sorts of growth signals and induces tumor cells growth,proliferation and metastasis.The double effect of Caveolin-1 in tumor is related to its signalings.This review will elaborate signalings regulated by Caveolin–1 in tumor cells.
引文
[1]Jasmin J F,Frank P G,Lisanti M P.Caveolins and caveolae:roles in signaling and disease mechanisms[M].New York:Springer,2012:381.
[2]Nabi I R,Le P U.Caveolae/raft-dependent endocytosis[J].J Cell Biol,2003,161(4):673-677.
[3]Sowa G.Caveolae,caveolins,cavins,and endothelial cell function:new insights[J].J Front Physiol,2011,2:120.
[4]Schubert W,Frank P G,Razani B,et al.Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo[J].J Biol Chem,2001,276(52):48 619-48 622.
[5]Calizo R C,Scarlata S.A role for G-proteins in directing G-proteincoupled receptor-caveolae localization[J].Biochemistry,2012,51(47):9513-9523.
[6]Patani N,Martin L A,Reis-Filho J S,et al.The role of caveolin-1 in human breast cancer[J].J Breast Cancer Res Treat,2012,131(1):1-15.
[7]Roy B,Upal K,Henkhaus R S,et al.Caveolin-1 is a novel regulator of K-RAS-dependent migration in colon carcinogenesis[J].J Int J Cancer,2013,133(1):43-57.
[8]Songserm T,Pongrakhananon V,Chanvorachote P.Sub-toxic cisplatin mediates anoikis resistance through hydrogen peroxideinduced Caveolin-1 up-regulation in non-small cell lung cancer cells[J].Anticancer Res,2012,32(5):1659-1669.
[9]Ochoa-Hernández A B,Juárez-Vázquez C I,Reynoso M A R,et al.WNT-β-catenin signaling pathway and its relationship with cancer[J].Cir Cir,2012,80(4):389-398.
[10]Lampugnani M G,Zanetti A,Corada M,et al.Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin,β-catenin,and the phosphatase DEP-1/CD148[J].J Cell Biol,2003,161(4):793-804.
[11]Galbiati F,Volonte D,Engelman J A,et al.Targeted downregulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade[J].EMBO J,1998,17(22):6633-6648.
[12]Ji J,Liu R,Tong T,et al.Gadd45a regulatesβ-catenin distribution and maintains cell-cell adhesion/contact[J].Oncogene,2007,26(44):6396-6405.
[13]Zhou L,Ercolano E,Ammoun S,et al.Merlin-deficient human tumors show loss of contact inhibition and activation of Wnt/β-catenin signaling linked to the PDGFR/Src and Rac/PAK pathways[J].Neoplasia,2011,13(12):1101.
[14]Singleton P A,Mirzapoiazova T,Guo Y,et al.High-molecularweight hyaluronan is a novel inhibitor of pulmonary vascular leakiness[J].Am J Physiol Lung Cell Mol Physiol,2010,299(5):L639-L651.
[15]Li L,Ren C H,Tahir S A,et al.Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A[J].Mol Cell Biol,2003,23(24):9389-9404.
[16]Kronstein R,Seebach J,Gro?klaus S,et al.Caveolin-1 opens endothelial cell junctions by targeting catenins[J].Cardiovasc Res,2012,93(1):130-140.
[17]Masuelli L,Budillon A,Marzocchella L,et al.Caveolin-1overexpression is associated with simultaneous abnormal expression of the E-cadherin/α-βcatenins complex and multiple erbb receptors and with lymph nodes metastasis in head and neck squamous cell carcinomas[J].J Cell Physiol,2012,227(9):3344-3353.
[18]王凯,李建远.Wnt/β-catenin信号通路与发育和疾病研究进展[J].中国医学创新,2012,9(11):160-161.
[19]Torres V A,Tapia J C,Rodriguez D A,et al.E-cadherin is required for caveolin-1-mediated down-regulation of the inhibitor of apoptosis protein survivin via reducedβ-catenin-Tcf/Lef-dependent transcription[J].Mol Cell Biol,2007,27(21):7703-7717.
[20]Steffens S,Schrader A,Blasig H,et al.Caveolin 1 protein expression in renal cell carcinoma predicts survival[J].BMC Urol,2011,11(1):25.
[21]Burgermeister E,Liscovitch M,R?cken C,et al.Caveats of caveolin-1 in cancer progression[J].Cancer letters,2008,268(2):187-201.
[22]Li L,Ren C H,Tahir S A,et al.Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A[J].Mol Cell Biol,2003,23(24):9389-9404.
[23]Drab M,Verkade P,Elger M,et al.Loss of caveolae,vascular dysfunction,and pulmonary defects in caveolin-1 gene-disrupted mice[J].Science,2001,293(5539):2449-2452.
[2]Nabi I R,Le P U.Caveolae/raft-dependent endocytosis[J].J Cell Biol,2003,161(4):673-677.
[3]Sowa G.Caveolae,caveolins,cavins,and endothelial cell function:new insights[J].J Front Physiol,2011,2:120.
[4]Schubert W,Frank P G,Razani B,et al.Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo[J].J Biol Chem,2001,276(52):48 619-48 622.
[5]Calizo R C,Scarlata S.A role for G-proteins in directing G-proteincoupled receptor-caveolae localization[J].Biochemistry,2012,51(47):9513-9523.
[6]Patani N,Martin L A,Reis-Filho J S,et al.The role of caveolin-1 in human breast cancer[J].J Breast Cancer Res Treat,2012,131(1):1-15.
[7]Roy B,Upal K,Henkhaus R S,et al.Caveolin-1 is a novel regulator of K-RAS-dependent migration in colon carcinogenesis[J].J Int J Cancer,2013,133(1):43-57.
[8]Songserm T,Pongrakhananon V,Chanvorachote P.Sub-toxic cisplatin mediates anoikis resistance through hydrogen peroxideinduced Caveolin-1 up-regulation in non-small cell lung cancer cells[J].Anticancer Res,2012,32(5):1659-1669.
[9]Ochoa-Hernández A B,Juárez-Vázquez C I,Reynoso M A R,et al.WNT-β-catenin signaling pathway and its relationship with cancer[J].Cir Cir,2012,80(4):389-398.
[10]Lampugnani M G,Zanetti A,Corada M,et al.Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin,β-catenin,and the phosphatase DEP-1/CD148[J].J Cell Biol,2003,161(4):793-804.
[11]Galbiati F,Volonte D,Engelman J A,et al.Targeted downregulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade[J].EMBO J,1998,17(22):6633-6648.
[12]Ji J,Liu R,Tong T,et al.Gadd45a regulatesβ-catenin distribution and maintains cell-cell adhesion/contact[J].Oncogene,2007,26(44):6396-6405.
[13]Zhou L,Ercolano E,Ammoun S,et al.Merlin-deficient human tumors show loss of contact inhibition and activation of Wnt/β-catenin signaling linked to the PDGFR/Src and Rac/PAK pathways[J].Neoplasia,2011,13(12):1101.
[14]Singleton P A,Mirzapoiazova T,Guo Y,et al.High-molecularweight hyaluronan is a novel inhibitor of pulmonary vascular leakiness[J].Am J Physiol Lung Cell Mol Physiol,2010,299(5):L639-L651.
[15]Li L,Ren C H,Tahir S A,et al.Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A[J].Mol Cell Biol,2003,23(24):9389-9404.
[16]Kronstein R,Seebach J,Gro?klaus S,et al.Caveolin-1 opens endothelial cell junctions by targeting catenins[J].Cardiovasc Res,2012,93(1):130-140.
[17]Masuelli L,Budillon A,Marzocchella L,et al.Caveolin-1overexpression is associated with simultaneous abnormal expression of the E-cadherin/α-βcatenins complex and multiple erbb receptors and with lymph nodes metastasis in head and neck squamous cell carcinomas[J].J Cell Physiol,2012,227(9):3344-3353.
[18]王凯,李建远.Wnt/β-catenin信号通路与发育和疾病研究进展[J].中国医学创新,2012,9(11):160-161.
[19]Torres V A,Tapia J C,Rodriguez D A,et al.E-cadherin is required for caveolin-1-mediated down-regulation of the inhibitor of apoptosis protein survivin via reducedβ-catenin-Tcf/Lef-dependent transcription[J].Mol Cell Biol,2007,27(21):7703-7717.
[20]Steffens S,Schrader A,Blasig H,et al.Caveolin 1 protein expression in renal cell carcinoma predicts survival[J].BMC Urol,2011,11(1):25.
[21]Burgermeister E,Liscovitch M,R?cken C,et al.Caveats of caveolin-1 in cancer progression[J].Cancer letters,2008,268(2):187-201.
[22]Li L,Ren C H,Tahir S A,et al.Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A[J].Mol Cell Biol,2003,23(24):9389-9404.
[23]Drab M,Verkade P,Elger M,et al.Loss of caveolae,vascular dysfunction,and pulmonary defects in caveolin-1 gene-disrupted mice[J].Science,2001,293(5539):2449-2452.