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The roles of p35/Cdk5 in cadherins/Beta-catenin-related adhesion in prostate cancer cells
|關鍵字:||prostate cancer;轉移;metastasis;migration;Cdk5;cadherin;遷移;細胞週期依靠激酶5;黏附蛋白||出版社:||生命科學系所||引用:||參考文獻  Peter Davidson, Should mass screening for prostate cancer be introduced at the national level?, WHO, 1(2004)1-12.  行政院衛生署, 92年衛生統計, 行政院衛生署 1(2003)78-82.  行政院衛生署, 92年衛生統計, 行政院衛生署 1(2003)133-137.  William F. Ganong, Review of Medical Physiology 9th, APPLETON & LANGE Stamford, Connecticut 1(1999)406-409.  J.T. Isaacs, E.R. Barrack, W.B. Isaacs, D.S. Coffey, The relationship of cellular structure and function: the matrix system, Prog Clin Biol Res 75A (1981) 1-24.  H. Bonkhoff, U. Stein, G. Aumuller, K. Remberger, Differential expression of 5 alpha-reductase isoenzymes in the human prostate and prostatic carcinomas, Prostate 29 (1996) 261-267.  P.A. Di Sant''Agnese, A.T. Cockett, The prostatic endocrine-paracrine (neuroendocrine) regulatory system and neuroendocrine differentiation in prostatic carcinoma: a review and future directions in basic research, J Urol 152 (1994) 1927-1931.  陳光國, 江漢聲, 張延驊, 攝護腺癌, 九州圖書文化有限公司1(1999)18-19.  N. Pecina-Slaus, Tumor suppressor gene E-cadherin and its role in normal and malignant cells, Cancer Cell Int 3 (2003) 17.  陳光國, 江漢聲, 張延驊, 攝護腺癌, 九州圖書文化有限公司1(1999) 29-31.  G.L. Lu-Yao, S.L. Yao, Population-based study of long-term survival in patients with clinically localised prostate cancer, Lancet 349 (1997) 906-910.  J.P. Thiery, M. Morgan, Breast cancer progression with a Twist, Nat. Med 8(2004) 777-778  Y. Kang, J. Massague, Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 118(2004) 277-279  A. Locascio, M.A. Nieto, Cell movements during vertebrate development: integrated tissue behaviour versus individual cell migration, Curr Opin Genet Dev 11 (2001) 464-469.  R. Horwitz, D. Webb, Cell migration, Curr Biol 13 (2003) R756-759.  D.A. Lauffenburger, A.F. Horwitz, Cell migration: a physically integrated molecular process, Cell 84 (1996) 359-369.  P. Friedl, K. Wolf, Tumour-cell invasion and migration: diversity and escape mechanisms, Nat Rev Cancer 3 (2003) 362-374.  L.D. Derycke, M.E. Bracke, N-cadherin in the spotlight of cell-cell adhesion, differentiation, embryogenesis, invasion and signalling, Int J Dev Biol 48 (2004) 463-476.  J.M. Gooding, K.L. Yap, M. Ikura, The cadherin-catenin complex as a focal point of cell adhesion and signalling: new insights from three-dimensional structures, Bioessays 26 (2004) 497-511.  A. Nagafuchi, Y. Shirayoshi, K. Okazaki, K. Yasuda, M. Takeichi, Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA, Nature 329 (1987) 341-343.  T. Volk, B. Geiger, A. Raz, Motility and adhesive properties of high- and low-metastatic murine neoplastic cells, Cancer Res 44 (1984) 811-824.  O.W. Rokhlin, M.B. Cohen, Expression of cellular adhesion molecules on human prostate tumor cell lines, Prostate 26 (1995) 205-212.  F. Hyafil, D. Morello, C. Babinet, F. Jacob, A cell surface glycoprotein involved in the compaction of embryonal carcinoma cells and cleavage stage embryos, Cell 21 (1980) 927-934.  D. Vestweber, R. Kemler, Rabbit antiserum against a purified surface glycoprotein decompacts mouse preimplantation embryos and reacts with specific adult tissues, Exp Cell Res 152 (1984) 169-178.  D. Riethmacher, V. Brinkmann, C. Birchmeier, A targeted mutation in the mouse E-cadherin gene results in defective preimplantation development, Proc Natl Acad Sci U S A 92 (1995) 855-859.  J. Yang, S.A. Mani, J.L. Donaher, S. Ramaswamy, R.A. Itzykson, C. Come, P. Savagner, I. Gitelman, A. Richardson, R.A. Weinberg, Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis, Cell 117 (2004) 927-939.  W.K. Kwok, M.T. Ling, T.W. Lee, T.C. Lau, C. Zhou, X. Zhang, C.W. Chua, K.W. Chan, F.L. Chan, C. Glackin, Y.C. Wong, X. Wang, Up-regulation of TWIST in prostate cancer and its implication as a therapeutic target, Cancer Res 65 (2005) 5153-5162.  A. Cano, M.A. Perez-Moreno, I. Rodrigo, A. Locascio, M.J. Blanco, M.G. del Barrio, F. Portillo, M.A. Nieto, The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression, Nat Cell Biol 2 (2000) 76-83.  E. Batlle, E. Sancho, C. Franci, D. Dominguez, M. Monfar, J. Baulida, A. Garcia De Herreros, The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells, Nat Cell Biol 2 (2000) 84-89.  S. Roura, S. Miravet, J. Piedra, A. Garcia de Herreros, M. Dunach, Regulation of E-cadherin/Catenin association by tyrosine phosphorylation, J Biol Chem 274 (1999) 36734-36740.  S. Potempa, A.J. Ridley, Activation of both MAP kinase and phosphatidylinositide 3-kinase by Ras is required for hepatocyte growth factor/scatter factor-induced adherens junction disassembly, Mol. Biol. Cell. 9(1998) 2185-2200.  J. Kamei, T. Toyofuku, M. Hori, Negative regulation of p21 by beta-catenin/TCF signaling: a novel mechanism by which cell adhesion molecules regulate cell proliferation, Biochem Biophys Res Commun 312 (2003) 380-387.  S. Islam, T.E. Carey, G.T. Wolf, M.J. Wheelock, K.R. Johnson, Expression of N-cadherin by human squamous carcinoma cells induces a scattered fibroblastic phenotype with disrupted cell-cell adhesion, J Cell Biol 135 (1996) 1643-1654.  K. Tomita, A. van Bokhoven, G.J. van Leenders, E.T. Ruijter, C.F. Jansen, M.J. Bussemakers, J.A. Schalken, Cadherin switching in human prostate cancer progression, Cancer Res 60 (2000) 3650-3654.  N.L. Tran, D.G. Adams, R.R. Vaillancourt, R.L. Heimark, Signal transduction from N-cadherin increases Bcl-2. Regulation of the phosphatidylinositol 3-kinase/Akt pathway by homophilic adhesion and actin cytoskeletal organization, J Biol Chem 277 (2002) 32905-32914.  Y.A. Gaidar, E.A. Lepekhin, G.A. Sheichetova, M. Witt, Distribution of N-cadherin and NCAM in neurons and endocrine cells of the human embryonic and fetal gastroenteropancreatic system, Acta Histochem 100 (1998) 83-97.  A.C. Han, A. Peralta-Soler, K.A. Knudsen, M.J. Wheelock, K.R. Johnson, H. Salazar, Differential expression of N-cadherin in pleural mesotheliomas and E-cadherin in lung adenocarcinomas in formalin-fixed, paraffin-embedded tissues, Hum Pathol 28 (1997) 641-645.  N.G. Ordonez, Value of E-cadherin and N-cadherin immunostaining in the diagnosis of mesothelioma, Hum Pathol 34 (2003) 749-755.  A.C. Han, A. Peralta-Soler, K.A. Knudsen, M.J. Wheelock, K.R. Johnson, H. Salazar, Differential expression of N-cadherin in pleural mesotheliomas and E-cadherin in lung adenocarcinomas in formalin-fixed, paraffin-embedded tissues, Hum Pathol 28 (1997) 641-645.  N.G. Ordonez, Value of E-cadherin and N-cadherin immunostaining in the diagnosis of mesothelioma, Hum Pathol 34 (2003) 749-755.  K. Asano, O. Kubo, Y. Tajika, K. Takakura, S. Suzuki, Expression of cadherin and CSF dissemination in malignant astrocytic tumors, Neurosurg Rev 23 (2000) 39-44.  R. Dhavan, L.H. Tsai, A decade of CDK5, Nat Rev Mol Cell Biol 2 (2001) 749-759.  M. Meyerson, G.H. Enders, C.L. Wu, L.K. Su, C. Gorka, C. Nelson, E. Harlow, L.H. Tsai, A family of human cdc2-related protein kinases, Embo J 11 (1992) 2909-2917.  J. Lew, K. Beaudette, C.M. Litwin, J.H. Wang, Purification and characterization of a novel proline-directed protein kinase from bovine brain, J Biol Chem 267 (1992) 13383-13390.  D. Tang, J. Yeung, K.Y. Lee, M. Matsushita, H. Matsui, K. Tomizawa, O. Hatase, J.H. Wang, An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator, J Biol Chem 270 (1995) 26897-26903.  S. Humbert, R. Dhavan, L. Tsai, p39 activates cdk5 in neurons, and is associated with the actin cytoskeleton, J Cell Sci 113 ( Pt 6) (2000) 975-983.  K.N. Beaudette, J. Lew, J.H. Wang, Substrate specificity characterization of a cdc2-like protein kinase purified from bovine brain, J Biol Chem 268 (1993) 20825-20830.  Z. Songyang, K.P. Lu, Y.T. Kwon, L.H. Tsai, O. Filhol, C. Cochet, D.A. Brickey, T.R. Soderling, C. Bartleson, D.J. Graves, A.J. DeMaggio, M.F. Hoekstra, J. Blenis, T. Hunter, L.C. Cantley, A structural basis for substrate specificities of protein Ser/Thr kinases: primary sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, CDK5, and Erk1, Mol Cell Biol 16 (1996) 6486-6493.  S. Kesavapany, K.F. Lau, D.M. McLoughlin, J. Brownlees, S. Ackerley, P.N. Leigh, C.E. Shaw, C.C. Miller, p35/cdk5 binds and phosphorylates beta-catenin and regulates beta-catenin/presenilin-1 interaction, Eur J Neurosci 13 (2001) 241-247.  M. Takeichi, K. Abe, Synaptic contact dynamics controlled by cadherin and catenins, Trends Cell Biol 15 (2005) 216-221.  K. Baumann, E.M. Mandelkow, J. Biernat, H. Piwnica-Worms, E. Mandelkow, Abnormal Alzheimer-like phosphorylation of tau-protein by cyclin-dependent kinases cdk2 and cdk5, FEBS Lett 336 (1993) 417-424.  K. Ishiguro, S. Kobayashi, A. Omori, M. Takamatsu, S. Yonekura, K. Anzai, K. Imahori, T. Uchida, Identification of the 23 kDa subunit of tau protein kinase II as a putative activator of cdk5 in bovine brain, FEBS Lett 342 (1994) 203-208.  G. Kato, S. Maeda, Neuron-specific Cdk5 kinase is responsible for mitosis-independent phosphorylation of c-Src at Ser75 in human Y79 retinoblastoma cells, J Biochem (Tokyo) 126 (1999) 957-961.  M. Nikolic, M.M. Chou, W. Lu, B.J. Mayer, L.H. Tsai, The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity, Nature 395 (1998) 194-198.  M. Nikolic, H. Dudek, Y.T. Kwon, Y.F. Ramos, L.H. Tsai, The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation, Genes Dev 10 (1996) 816-825.  D.B. Evans, K.B. Rank, K. Bhattacharya, D.R. Thomsen, M.E. Gurney, S.K. Sharma, Tau phosphorylation at serine 396 and serine 404 by human recombinant tau protein kinase II inhibits tau''s ability to promote microtubule assembly, J Biol Chem 275 (2000) 24977-24983.  Y.T. Kwon, A. Gupta, Y. Zhou, M. Nikolic, L.H. Tsai, Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 kinase, Curr Biol 10 (2000) 363-372.  N. Ratner, G.S. Bloom, S.T. Brady, A role for cyclin-dependent kinase(s) in the modulation of fast anterograde axonal transport: effects defined by olomoucine and the APC tumor suppressor protein, J Neurosci 18 (1998) 7717-7726.  M. Mapelli, A. Musacchio, The structural perspective on CDK5, Neurosignals 12 (2003) 164-172.  T. Sandal, C. Stapnes, H. Kleivdal, L. Hedin, S.O. Doskeland, A novel, extraneuronal role for cyclin-dependent protein kinase 5 (CDK5): modulation of cAMP-induced apoptosis in rat leukemia cells, J Biol Chem 277 (2002) 20783-20793.  N. Nakano, A. Nakao, K. Ishidoh, R. Tsuboi, E. Kominami, K. Okumura, H. Ogawa, CDK5 regulates cell-cell and cell-matrix adhesion in human keratinocytes, Br J Dermatol 153 (2005) 37-45.  E.M. Schuman, S. Murase, Cadherins and synaptic plasticity: activity-dependent cyclin-dependent kinase 5 regulation of synaptic beta-catenin-cadherin interactions, Philos Trans R Soc Lond B Biol Sci 358 (2003) 749-756.  J.M. Wang, T. Hayashi, W.R. Zhang, K. Sakai, Y. Shiro, K. Abe, Insulin-like growth factor-1 affects expressions of cyclin-dependent kinase 5 and its activator p35 in reperfused rat brain, Neurosci Lett 277 (1999) 17-20.  M.P. Playford, D. Bicknell, W.F. Bodmer, V.M. Macaulay, Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin, Proc Natl Acad Sci U S A 97 (2000) 12103-12108.  A.E. Vernon, C. LaBonne, Tumor metastasis: a new twist on epithelial-mesenchymal transitions, Curr Biol 14 (2004) R719-721.  M.L. Davies, G.T. Roberts, D.G. Spiller, J.A. Wakeman, Density-dependent location and interactions of truncated APC and beta-catenin, Oncogene 23 (2004) 1412-1419.  C.Y. Gao, M.A. Stepp, R. Fariss, P. Zelenka, Cdk5 regulates activation and localization of Src during corneal epithelial wound closure, J Cell Sci 117 (2004) 4089-4098.  P. Savagner, D.F. Kusewitt, E.A. Carver, F. Magnino, C. Choi, T. Gridley, L.G. Hudson, Developmental transcription factor slug is required for effective re-epithelialization by adult keratinocytes, J Cell Physiol 202 (2005) 858-866.  A. Grimberg, Mechanisms by which IGF-I may promote cancer, Cancer Biol Ther 2 (2003) 630-635.  H. Lin, J.L. Juang, P.S. Wang, Involvement of Cdk5/p25 in digoxin-triggered prostate cancer cell apoptosis, J Biol Chem 279 (2004) 29302-29307.  C. Gao, S. Negash, H.T. Guo, D. Ledee, H.S. Wang, P. Zelenka, CDK5 regulates cell adhesion and migration in corneal epithelial cells, Mol. Cancer. Res. 1(2002) 12-24.  B.S. Li, W. Ma, H. Jaffe, Y. Zheng, S. Takahashi, L. Zhang, A.B. Kulkarni, H.C. Pant, Cyclin-dependent kinase-5 is involved in neuregulin-dependent activation of phosphatidylinositol 3-kinase and Akt activity mediating neuronal survival, J Biol Chem 278 (2003) 35702-35709.  J.N. Yu, S.F. Ma, D.Q. Miao, X.W. Tan, X.Y. Liu, J.H.Lu and J.H. Tan, Effects of cell cycle status on the efficiency of liposome-mediated gene transfection in mouse fetal fibroblasts, J. Reprod. Dev. 52(2006) 373-82.||摘要:||
根據民國九十二年衛生署衛生統計資料，國人攝護腺癌(prostate cancer)發生率與死亡率有逐年上升趨勢，而相較於其它癌症的死亡個案，攝護腺癌死亡個案佔癌症總數的比例，也逐年上升。攝護腺癌轉移為攝護腺癌主要死因。一般癌細胞轉移可分為五個步驟，包括侵入(invasion)、滲入(intravasation)、滲出(extravasation)、微量轉移(micrometastasis)、巨大轉移(macrometastasis)，癌細胞在侵入的過程為上皮-間葉轉變(epithelial-mesenchymal transition)，最初始的階段即是必須打破細胞間的黏附接合(adhering junction)。黏附接合為細胞與細胞間主要的連接，其中E-cadherin/β-catenin為調控上皮細胞黏附接合主要複合體，N-cadherin/β-catenin為調控神經細胞黏附接合主要複合體，此外N-cadherin/β-catenin複合體也表現在一些癌細胞中。在上皮-間葉轉變中，E-cadherin為上皮標記(epithelial marker)，N-cadherin為間葉標記(mesenchymal marker)。
Cdk5為絲胺酸(serine)與蘇胺酸(threonine)激酶(kinase)，屬於Cdk家族，而p35為其activator。根據前人研究發現，在神經細胞內Cdk5可藉由p35與β-catenin接合，並且導致間接β-catenin之tyrosine磷酸化，使得N-cadherin/β-catenin複合體分離。抑制Cdk5活性，在神經細胞可使得N-cadherin與β-catenin連接增加；在角質細胞可使得藉由E-cadherin與β-catenin調控堆疊增加；另外，過度表現兔子水晶體上皮細胞Cdk5可減少界面活性劑不可溶性蛋白(detergent insoluble protein) N-cadherin表現。
人類攝護腺癌細胞株PC-3為同時表現N-cadherin與E-cadherin。在本篇論文研究中，證實PC3細胞內Cdk5/p35與β-catenin有交互作用。抑制Cdk5活性可抑制PC-3損傷癒合(wound closure assay)，其最主要的機制為增加不可溶性E-cadherin的表現量與減少Filopodium的生成，並且利用siRNA-Cdk5抑制Cdk5的表現可增加界面活性劑不可溶性蛋白E-cadherin與β-catenin的表現。此外，Igf-1(insulin like growth factor-1，類胰島生長激素)為一穩定p35的生長激素，在本篇論文研究中發現，Igf-1處理PC-3細胞可以減少界面活性劑不可溶性E-cadherin、N-cadherin表現，但經由Cdk5抑制劑處理，可回復界面活性劑不可溶性E-cadherin、N-cadherin表現。由此，我們可以推測在PC-3細胞株中，Cdk5活性與癌細胞黏附接合以及細包移動相關。
The incidence and mortality of prostate cancer was increased in progress in Taiwan. The metastasis of prostate cancer is the key of mortality. The five steps of metastasis include invasion, intravasation, extravasation, micrometastasis and macrometastasis. The initiation step of metastasis is called invasion in which includes EMT (epithelial-mesenchymal transition) and dissociation of cell and cell adherent junction via the regulation of cadherins/β-catenin complex. E-cadherin is expression in epithelial cells and N-cadherin is expression in neural cells. E-cadherin is also considered as epithelial marker and N-cadherin is which for mesenchymal marker.
Cdk5/p35 complex is a serine/threonine kinase. It has been reported that p35, an activator of Cdk5, associates with both N-cadherin/β-catenin complex in neuronal cells and E-cadherin/β-catenin complex in human keratinocytes. p35 overexpression could result in disassociation of N-cadherin/β-catenin complex. In the other hand, inhibition of Cdk5/p35 activity led to increase N-cadherin-mediated adhesion in neuronal cells and E-cadherin-mediated adhesion in human keratinocytes, respectively. In addition, Cdk5 overexpression could reduce expression of detergent-insoluble N-cadherin in rabbit lens epithelial cells.
Our strategy is taking advantage of cell culture system of prostate cancer cell line, PC-3, which contains both N- and E-cadherin protein expressions. The present results demonstrated that, Cdk5 inhibition by treatment of roscovitine (RV) could reduce cell migration measured by wound closure assay. The molecular mechanism was addressed on the rising expression of detergent-insoluble E-cadherin. In addition, transfected siRNA-Cdk5 in PC-3 cells could reduce expression of Cdk5 and increase expression of detergent-insoluble E-cadherin and β-catenin. On the other hand, detergent-insoluble N-cadherin, E-cadherin and β-catenin in PC-3 cells were down-regulated by treatment with insulin-like growth factor 1 (IGF-1, as a stabilizer of p35 protein). In addition, the IGF-1-dependent effects above could be reversed by treatment of RV. In conclusion, we suggest that p35/Cdk5 might play an important role in regulating cadherin/β-catenin-related adhesion and cell migration in prostate cancer cells.
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