Abstract
High-throughput (HT) proteomic techniques allow the study of hundreds to thousands of proteins simultaneously. Several HT methodologies have been developed to determine protein-protein interactions (PPIs) and therefore protein function in mammalian cells. A few of these, including protein complementation assays, mass spectrometry, yeast two-hybrid and luminescence-based mammalian interactome (LUMIER) mapping, have been applied to the study of TGFβ signaling. PPIs revealed with these techniques have been crucial in elucidating novel components of the TGFβ signaling network involved in tissue homeostasis and cancer. A good example of this is the recently described TGFβ/Par6 polarity pathway, which was initially discovered in a LUMIER screen for PPIs. A role of this pathway in the process of epithelial-mesenchymal transition has been demonstrated, suggesting its potential involvement in cancer metastasis. Thus, proteomic data are becoming an essential tool for unraveling the dynamic networks that drive cancer onset and tumor progression.
These authors contributed equally to this work.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Barrios-Rodiles M, Brown KR, Ozdamar B, et al. High-throughput mapping of a dynamic signaling network in mammalian cells. Science 2005;307:1621–1625.
Eyckerman S, Verhee A, der Heyden JV, et al. Design and application of a cytokine-receptor-based interaction trap. Nat Cell Biol 2001;3:1114–1119.
Boute N, Jockers R, Issad T. The use of resonance energy transfer in high-throughput screening: BRET versus PRET. Trends Pharmacol Sci 2002;23:351–354.
Michnick SW. Protein fragment complementation strategies for biochemical network mapping. Curr Opin Biotechnol 2003;14:610–617.
Schweitzer B, Predki P, Snyder M. Microarrays to characterize protein interactions on a whole-proteome scale. Proteomics 2003;3:2190–2199.
Uetz P, Hughes RE. Systematic and large-scale two-hybrid screens. Curr Opin Microbiol 2000;3: 303–308.
Gavin AC, Superti-Furga G. Protein complexes and proteome organization from yeast to man. Curr Opin Chem Biol 2003;7:21–27.
Rossi F, Charlton CA, Blau HM. Monitoring protein-protein interactions in intact eukaryotic cells by beta-galactosidase complementation. Proc Natl Acad Sci USA 1997;94:8405–8410.
Hu CD, Chinenov Y, Kerppola TK. Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. Mol Cell 2002;9:789–798.
Remy I, Michnick SW. Visualization of biochemical networks in living cells. Proc Natl Acad Sci USA 2001;98:7678–7683.
Hu CD, Kerppola TK. Simultaneous visualization of multiple protein interactions in living cells using multicolor fluorescence complementation analysis. Nat Biotechnol 2003;21:539–545.
Remy I, Michnick SW. Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt. Mol Cell Biol 2004;24:1493–1504.
Remy I, Montmarquette A, Michnick SW. PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3. Nat Cell Biol 2004;6:358–365.
Conery AR, Cao Y, Thompson EA, Townsend CM, Jr, Ko TC, Luo K. Akt interacts directly with Smad3 to regulate the sensitivity to TGF-beta induced apoptosis. Nat Cell Biol 2004;6:366–372.
Song K, Wang H, Krebs TL, Danielpour D. Novel roles of Akt and mTOR in suppressing TGF-beta/ALK5-mediated Smad3 activation. EMBO J 2006;25:58–69.
Roberts AB, Wakefield LM. The two faces of transforming growth factor beta in carcinogenesis. Proc Natl Acad Sci USA 2003;100:8621–8623.
Shaner NC, Steinbach PA, Tsien RY. A guide to choosing fluorescent proteins. Nat Methods 2005;2: 905–909.
Gingras AC, Aebersold R, Raught B. Advances in protein complex analysis using mass spectrometry. J Physiol 2005;563:11–21.
Ho Y, Gruhler A, Heilbut A, et al. Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 2002;415:180–183.
Rigaut G, Shevchenko A, Rutz B, Wilm M, Mann M, Seraphin B. A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol 1999;17: 1030–1032.
Gavin AC, Bosche M, Krause R, et al. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 2002;415:141–147.
Gavin AC, Aloy P, Grandi P, et al. Proteome survey reveals modularity of the yeast cell machinery. Nature 2006;400:631–636.
Bouwmeester T, Bauch A, Ruffner H, et al. A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nat Cell Biol 2004;6:97–105.
Brajenovic M, Joberty G, Kuster B, Bouwmeester T, Drewes G. Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network. J Biol Chem 2004;279: 12,804–12,811.
Knuesel M, Wan Y, Xiao Z, et al. Identification of novel protein-protein interactions using a versatile mammalian tandem affinity purification expression system. Mol Cell Proteomics 2003;2:1225–1233.
Stroschein SL, Wang W, Zhou S, Zhou Q, Luo K. Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein. Science 1999;286:771–774.
Grimsby S, Jaensson H, Dubrovska A, Lomnytska M, Hellman U, Souchelnytskyi S. Proteomics-based identification of proteins interacting with Smad3: SREBP-2 forms a complex with Smad3 and inhibits its transcriptional activity. FEBS Lett 2004;577:93–100.
Mann M, Jensen ON. Proteomic analysis of post-translational modifications. Nat Biotechnol 2003; 21:255–261.
Stasyk T, Dubrovska A, Lomnytska M, et al. Phosphoproteome profiling of transforming growth factor (TGF)-beta signaling: abrogation of TGFbeta1-dependent phosphorylation of transcription factor-II-I (TFII-I) enhances cooperation of TFII-I and Smad3 in transcription. Mol Biol Cell 2005; 16:4765–4780.
Schwartz GK, Shah MA. Targeting the cell cycle: a new approach to cancer therapy. J Clin Oncol 2005;23:9408–9421.
DeGregori J. The genetics of the E2F family of transcription factors: shared functions and unique roles. Biochim Biophys Acta 2002;1602:131–150.
Ong SE, Blagoev B, Kratchmarova I, et al. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 2002;1: 376–386.
Blagoev B, Ong SE, Kratchmarova I, Mann M. Temporal analysis of phosphotyrosine-dependent signaling networks by quantitative proteomics. Nat Biotechnol 2004;22:1139–1145.
Attisano L, Wrana JL. Signal transduction by the TGF-beta superfamily. Science 2002;296:1646–1647.
Uetz P, Finley RL, Jr. From protein networks to biological systems. FEBS Lett 2005;579:1821–1827.
McCraith S, Holtzman T, Moss B, Fields S. Genome-wide analysis of vaccinia virus protein-protein interactions. Proc Natl Acad Sci USA 2000;97:4879–4884.
Schwikowski B, Uetz P, Fields S. A network of protein-protein interactions in yeast. Nat Biotechnol 2000;18:1257–1261.
Uetz P, Giot L, Cagney G, et al. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 2000;403:623–627.
Li S, Armstrong CM, Bertin N, et al. A map of the interactome network of the metazoan C. elegans. Science 2004;303:540–543.
Giot L, Bader JS, Brouwer C, et al. A protein interaction map of Drosophila melanogaster. Science 2003;302:1727–1736.
Stelzl U, Worm U, Lalowski M, et al. A human protein-protein interaction network: a resource for annotating the proteome. Cell 2005;122:957–968.
Rual JF, Venkatesan K, Hao T, et al. Towards a proteome-scale map of the human protein-protein interaction network. Nature 2005;437:1173–1178.
Vidal M, Legrain P. Yeast forward and reverse ‘n’-hybrid systems. Nucleic Acids Res 1999;27:919–929.
Legrain P, Wojcik J, Gauthier JM. Protein-protein interaction maps: a lead towards cellular functions. Trends Genet 2001;17:346–352.
Uetz P. Two-hybrid arrays. Curr Opin Chem Biol 2002;6:57–62.
Drewes G, Bouwmeester T. Global approaches to protein-protein interactions. Curr Opin Cell Biol 2003;15:199–205.
Aronheim A, Zandi E, Hennemann H, Elledge SJ, Karin M. Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions. Mol Cell Biol 1997;17:3094–3102.
Vidalain PO, Boxem M, Ge H, Li S, Vidal M. Increasing specificity in high-throughput yeast twohybrid experiments. Methods 2004;32:363–370.
Stagljar I, Korostensky C, Johnsson N, te Heesen S. A genetic system based on split-ubiquitin for the analysis of interactions between membrane proteins in vivo. Proc Natl Acad Sci USA 1998;95: 5187–5192.
Fearon ER, Finkel T, Gillison ML, et al. Karyoplasmic interaction selection strategy: a general strategy to detect protein-protein interactions in mammalian cells. Proc Natl Acad Sci USA 1992;89:7958–7962.
Tewari M, Hu PJ, Ahn JS, et al. Systematic interactome mapping and genetic perturbation analysis of a C. elegans TGF-beta signaling network. Mol Cell 2004;13:469–482.
Macias-Silva M, Li W, Leu JI, Crissey MA, Taub R. Up-regulated transcriptional repressors SnoN and Ski bind Smad proteins to antagonize transforming growth factor-beta signals during liver regeneration. J Biol Chem 2002;277:28,483–28,490.
Chen YG, Shields D. ADP-ribosylation factor-1 stimulates formation of nascent secretory vesicles from the trans-Golgi network of endocrine cells. J Biol Chem 1996:271:5297–5300.
Colland F, Jacq X, Trouplin V, et al. Functional proteomics mapping of a human signaling pathway. Genome Res 2004;14:1324–1332.
Shi W, Sun C, He B, et al. GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. J Cell Biol 2004;164:291–300.
Jiao K, Zhou Y, Hogan BL. Identification of mZnf8, a mouse Kruppel-like transcriptional repressor, as a novel nuclear interaction partner of Smad1. Mol Cell Biol 2002;22:7633–7644.
Lin F, Morrison JM, Wu W, Worman HJ. MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling. Hum Mol Genet 2005;14:437–445.
Subramaniam V, Li H, Wong M, et al. The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase. Br J Cancer 2003;89:1538–1544.
Azmi P, Seth A. RNF11 is a multifunctional modulator of growth factor receptor signalling and transcriptional regulation. Eur J Cancer 2005;41:2549–2560.
Visvader JE, Venter D, Hahm K, et al. The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer. Proc Natl Acad Sci USA 2001;98: 14,452–14,457.
Lu Z, Lam KS, Wang N, Xu X, Cortes M, Andersen B. LMO4 can interact with Smad proteins and modulate transforming growth factor-beta signaling in epithelial cells. Oncogene 2006;25:2920–2930.
Ito T, Chiba T, Ozawa R, Yoshida M, Hattori M, Sakaki Y. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad Sci USA 2001;98:4569–4574.
Russ AP, Lampel S. The druggable genome: an update. Drug Discov Today 2005;10:1607–1610.
Stagljar I, Fields S. Analysis of membrane protein interactions using yeast-based technologies. Trends Biochem Sci 2002;27:559–563.
Siegel PM, Massagué J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer 2003;3:807–821.
Pawson T. Specificity in signal transduction: from phosphotyrosine-SH2 domain interactions to complex cellular systems. Cell 2004;116:191–203.
Feng XH, Derynck R. Specificity and versatility in TGF-beta signaling through Smads. Annu Rev Cell Dev Biol 2005;21:659–693.
Abdollah S, Macias-Silva M, Tsukazaki T, Hayashi H, Attisano L, Wrana JL. TbetaRI phosphorylation of Smad2 on Ser465 and Ser467 is required for Smad2-Smad4 complex formation and signaling. J Biol Chem 1997;272:27,678–27,685.
Aderem A. Systems biology: its practice and challenges. Cell 2005;121:511–513.
Sultan M, Wigle DA, Cumbaa CA, et al. Binary tree-structured vector quantization approach to clustering and visualizing microarray data. Bioinformatics 2002;18 Suppl 1:S111–S119.
Bokoch GM. Biology of the p21-activated kinases. Annu Rev Biochem 2003;72:743–781.
Wilkes MC, Murphy SJ, Garamszegi N, Leof EB. Cell-type-specific activation of PAK2 by transforming growth factor beta independent of Smad2 and Smad3. Mol Cell Biol 2003;23:8878–8889.
Chen W, Yazicioglu M, Cobb MH. Characterization of OSR1, a member of the mammalian Ste20p/germinal center kinase subfamily. J Biol Chem 2004;279:11,129–11,136.
Feldman GJ, Mullin JM, Ryan MP. Occludin: structure, function and regulation. Adv Drug Deliv Rev 2005;57:883–917.
Rhodes DR, Chinnaiyan AM. Integrative analysis of the cancer transcriptome. Nat Genet 2005;37: Suppl:S31–S37.
Brown KR, Jurisica I. Online predicted human interaction database. Bioinformatics 2005;21:2076–2082.
Bader GD, Donaldson I, Wolting C, Ouellette BF, Pawson T, Hogue CW. BIND — The Biomolecular Interaction Network Database. Nucleic Acids Res 2001;29:242–245.
Peri S, Navarro JD, Amanchy R, et al. Development of human protein reference database as an initial platform for approaching systems biology in humans. Genome Res 2003;13:2363–2371.
Poste G, Fidler IJ. The pathogenesis of cancer metastasis. Nature 1980;283:139–146.
Liotta LA, Kohn EC. Cancer’s deadly signature. Nat Genet 2003;33:10–11.
Bissell MJ, Labarge MA. Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment? Cancer Cell 2005;7:17–23.
Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nat Genet 2003;33:49–54.
Zavadil J, Bottinger EP. TGF-beta and epithelial-to-mesenchymal transitions. Oncogene 2005;24: 5764–5774.
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100:57–70.
Oft M, Peli J, Rudaz C, Schwarz H, Beug H, Reichmann E. TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev 1996;10:2462–2477.
Putz E, Witter K, Offner S, et al. Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases. Cancer Res 1999;59:241–248.
Thiery JP. Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol 2003;15:740–746.
Huber MA, Azoitei N, Baumann B, et al. NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest 2004;114:569–581.
Willipinski-Stapelfeldt B, Riethdorf S, Assmann V, et al. Changes in cytoskeletal protein composition indicative of an epithelial-mesenchymal transition in human micrometastatic and primary breast carcinoma cells. Clin Cancer Res 2005;11:8006–8014.
Welch DR, Fabra A, Nakajima M. Transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential. Proc Natl Acad Sci USA 1990;87:7678–7682.
Bandyopadhyay A, Zhu Y, Cibull ML, Bao L, Chen C, Sun L. A soluble transforming growth factor beta type III receptor suppresses tumorigenicity and metastasis of human breast cancer MDA-MB-231 cells. Cancer Res 1999;59:5041–5046.
Bandyopadhyay A. Lopez-Casillas F, Malik SN, et al. Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft. Cancer Res 2002;62:4690–4695.
Yang YA, Dukhanina O, Tang B, et al. Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. J Clin Invest 2002;109:1607–1615.
Muraoka RS, Dumont N, Ritter CA, et al. Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest 2002;109:1607–1615.
Muraoka RS, Koh Y, Roebuck LR, et al. Increased malignancy of Neu-induced mammary tumors overexpressing active transforming growth factor beta1. Mol Cell Biol 2003;23:8691–8703.
Siegel PM, Shu W, Cardiff RD, Muller WJ, Massagué J. Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci USA 2003;100:8430–8435.
Tang B, Vu M, Booker T, et al. TGF-beta switches from tumor suppressor to prometastatic factor in a model of breast cancer progression. J Clin Invest 2003;112:1116–1124.
Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol 2005;17:548–558.
Dandachi N, Hauser-Kronberger C, More E, et al. Co-expression of tenascin-C and vimentin in human breast cancer cells indicates phenotypic transdifferentiation during tumour progression: correlation with histopathological parameters, hormone receptors, and oncoproteins. J Pathol 2001;193: 181–189.
Muraoka-Cook RS, Dumont N, Arteaga CL. Dual role of transforming growth factor beta in mammary tumorigenesis and metastatic progression. Clin Cancer Res 2005;11:937s–943s.
Dalal BI, Keown PA, Greenberg AH. Immunocytochemical localization of secreted transforming growth factor-beta 1 to the advancing edges of primary tumors and to lymph node metastases of human mammary carcinoma. Am J Pathol 1993;143:381–389.
Chakravarthy D, Green AR, Green VL, Kerin MJ, Speirs V. Expression and secretion of TGF-beta isoforms and expression of TGF-beta-receptors I, II and III in normal and neoplastic human breast. Int J Oncol 1999;15:187–194.
Desruisseau S, Palmari J, Giusti C, Romain S, Martin PM, Berthois Y. Determination of TGFbeta1 protein level in human primary breast cancers and its relationship with survival. Br J Cancer 2006; 94:239–246.
van’t Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 2002;415:530–536.
van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002;347:1999–2009.
Zavadil J, Bitzer M, Liang D, et al. Genetic programs of epithelial cell plasticity directed by transforming growth factor-beta. Proc Natl Acad Sci USA 2001;98:6686–6691.
Jechlinger M, Grunert S, Tamir IH, et al. Expression profiling of epithelial plasticity in tumor progression. Oncogene 2003;22:7155–7169.
Valcourt U, Kowanetz M, Niimi H, Heldin C-H, Moustakas A. TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol Biol Cell 2005;16:1987–2002.
Michiels S, Koscielny S, Hill C. Prediction of cancer outcome with microarrays: a multiple random validation strategy. Lancet 2005;365:488–492.
Segal E, Wang H, Koller D. Discovering molecular pathways from protein interaction and gene expression data. Bioinformatics 2003;19 Suppl 1:i264–i271.
Segal E, Shapira M, Regev A, et al. Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data. Nat Genet 2003;34:166–176.
Segal E, Friedman N, Kaminski N, Regev A, Koller D. From signatures to models: understanding cancer using microarrays. Nat Genet 2005;37 Suppl:S38–S45.
Ohno S. Intercellular junctions and cellular polarity: the PAR-aPKC complex, a conserved core cassette playing fundamental roles in cell polarity. Curr Opin Cell Biol 2001;13:641–648.
Bissell MJ, Bilder D. Polarity determination in breast tissue: desmosomal adhesion, myoepithelial cells, and laminin 1. Breast Cancer Res 2003;5:117–119.
Watts JL, Etemad-Moghadam B, Guo S, et al. par-6, a gene involved in the establishment of asymmetry in early C. elegans embryos, mediates the asymmetric localization of PAR-3. Development 1996; 122:3133–3140.
Etienne-Manneville S, Hall A. Cell polarity: Par6, aPKC and cytoskeletal crosstalk. Curr Opin Cell Biol 2003;15:67–72.
Bose R, Wrana JL. Regulation of Par6 by extracellular signals. Curr Opin Cell Biol 2006;18: 206–212.
Roh MH, Margolis B. Composition and function of PDZ protein complexes during cell polarization. Am J Physiol Renal Physiol 2003;285:F377–F387.
Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y, Wrana JL. Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science 2005;307:1603–1609.
Seton-Rogers SE, Lu Y, Hines LM, et al. Cooperation of the ErbB2 receptor and transforming growth factor beta in induction of migration and invasion in mammary epithelial cells. Proc Natl Acad Sci USA 2004;101:1257–1262.
Ueda Y, Wang S, Dumont N, Yi JY, Koh Y, Arteaga CL. Overexpression of HER2 (erbB2) in human breast epithelial cells unmasks transforming growth factor beta-induced cell motility. J Biol Chem 2004;279:24,505–24,513.
Zhou BP, Deng J, Xia W, et al. Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol 2004;6:931–940.
Ohkubo T, Ozawa M. The transcription factor Snail downregulates the tight junction components independently of E-cadherin downregulation. J Cell Sci 2004;117:1675–1685.
Blanco MJ, Moreno-Bueno G, Sarrio D, et al. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene 2002;21:3241–3246.
Moody SE, Perez D, Pan TC, et al. The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell 2005;8:197–209.
Bakin AV, Tomlinson AK, Bhowmick NA, Moses HL, Arteaga CL. Phosphatidylinositol 3-kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition and cell migration. J Biol Chem 2000;275:36,803–36,810.
von Stein W, Ramrath A, Grimm A, Muller-Borg M, Wodarz A. Direct association of Bazooka/PAR-3 with the lipid phosphatase PTEN reveals a link between the PAR/aPKC complex and phosphoinositide signaling. Development 2005;132:1675–1686.
Kanzaki M, Mora S, Hwang JB, Saltiel, AR, Pessin JE. Atypical protein kinase C (PKCzeta/lambda) is a convergent downstream target of the insulin-stimulated phosphatidylinositol, 3-kinase and TC10 signaling pathways. J Cell Biol 2004;164:279–290.
Aranda V, Haire T, Nolan ME, et al. Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control. Nat Cell Biol 2006;8:1235–1245.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Humana Press Inc., Totowa, NJ
About this chapter
Cite this chapter
Barrios-Rodiles, M., Viloria-Petit, A., Brown, K.R., Jurisica, I., Wrana, J.L. (2008). High-Throughput Screening of Protein Interaction Networks in the TGFβ Interactome: Understanding the Signaling Mechanisms Driving Tumor Progression. In: Jakowlew, S.B. (eds) Transforming Growth Factor-β in Cancer Therapy, Volume II. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-293-9_18
Download citation
DOI: https://doi.org/10.1007/978-1-59745-293-9_18
Publisher Name: Humana Press
Print ISBN: 978-1-58829-715-0
Online ISBN: 978-1-59745-293-9
eBook Packages: MedicineMedicine (R0)