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Unravelling of Hidden Secrets: The Tumour Suppressor Lethal (2) Giant Discs (Lgd)/CC2D1, Notch Signalling and Cancer

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Notch Signaling in Embryology and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1287))

Abstract

The endosomal pathway plays a pivotal role upon signal transduction in the Notch pathway. Recent work on lethal (2) giant discs (lgd) points to an additional critical role in avoiding uncontrolled ligand-independent signalling during trafficking of the Notch receptor through the endosomal pathway to the lysosome for degradation. In this chapter, we will outline the journey of Notch through the endosomal system and present an overview of the current knowledge about Lgd and its mammalian orthologs Lgd1/CC2D1b and Lgd2/CC2D1a. We will then discuss how Notch is activated in the absence of lgd function in Drosophila and ask whether there is evidence that a similar ligand-independent activation of the Notch pathway can also happen in mammals if the orthologs are inactivated.

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References

  • Adell M, Migliano SM, Upadhyayula S, Bykov YS, Sprenger S, Pakdel M, Vogel GF, Jih G, Skillern W, Behrouzi R, Babst M, Schmidt O, Hess MW, Briggs JA, Kirchhausen T, Teis D (2017) Recruitment dynamics of ESCRT-III and Vps4 to endosomes and implications for reverse membrane budding. eLife. 2017; 6:e31652

    Google Scholar 

  • Al-Tawashi A, Jung SY, Liu D, Su B, Qin J (2012) Protein implicated in nonsyndromic mental retardation regulates protein kinase A (PKA) activity. J Biol Chem 287:14544–14558

    Article  CAS  Google Scholar 

  • Arnett KL, Seegar TCM, Blacklow SC (2018) Structural biology of Notch signaling. In: Miele L, Artavanis-Tsakonas S (eds) Targeting Notch in cancer. Springer Science+Business Media, LLC, part of Springer Nature 2018

    Google Scholar 

  • Aster JC, Pear WS, Blacklow SC (2017) The varied roles of Notch in cancer. Annu Rev Pathol Mech Dis 12:245–275

    Article  CAS  Google Scholar 

  • Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–1007

    Article  CAS  PubMed  Google Scholar 

  • Basel-Vanagaite L, Attia R, Yahav M, Ferland RJ, Anteki L, Walsh CA, Olender T, Straussberg R, Magal N, Taub E, Drasinover V, Alkelai A, Bercovich D, Rechavi G, Simon AJ, Shohat M (2006) The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non-syndromic mental retardation. J Med Genet 43:203–210

    Article  CAS  PubMed  Google Scholar 

  • Bäumers M, Klose S, Brüser C, Haag C, Hänsch S, Pannen H, Weidtkamp-Peters S, Feldbrügge M, Klein T (2019) The auxiliary ESCRT complexes provide robustness to cold in poikilothermic organisms. Biology Open 2019 8:bio043422

    Google Scholar 

  • Berndt N, Seib E, Kim S, Troost T, Lyga M, Langenbach J, Haensch S, Kalodimou K, Delidakis C, Klein T (2017) Ubiquitylation-independent activation of Notch signalling by Delta. Elife. 2017 Sep 29;6:e27346

    Google Scholar 

  • Bryant PJ, Schubiger G (1971) Giant and duplicated imaginal discs in a new lethal mutant of Drosophila melanogaster. Dev Biol 24:233–263

    Article  CAS  PubMed  Google Scholar 

  • Buratovich MA, Bryant PJ (1997) Enhancement of overgrowth by gene interactions in lethal(2)giant discs imaginal discs from Drosophila melanogaster. Genetics 147:657–670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang C-H, Lai L-C, Cheng H-C, Chen K-R, Syue Y-Z, Lu H-C, Lin W-Y, Chen S-H, Huang H-S, Shiau A-L, Lei H-Y, Qin J, Ling P (2011) TBK1-associated Protein in Endolysosomes (TAPE) is an innate immune regulator modulating the TLR3 and TLR4 signaling pathways. JBC 286:7043–7051

    Article  CAS  Google Scholar 

  • Chastagner P, Israel A, Brou C (2008) AIP4/Itch regulates Notch receptor degradation in the absence of ligand. PLoS ONE 3(7):e2735

    Google Scholar 

  • Chastagner P, Rubinstein E, Brou C (2017) Ligand-activated Notch undergoes DTX4-mediated ubiquitylation and bilateral endocytosis before ADAM10 processing. Sci Signal 10:1–13

    Article  CAS  Google Scholar 

  • Chen KR, Chang CH, Huang CY, Lin CY, Lin WY, Lo YC, Yang CY, Hsing EW, Chen LF, Shih SR, Shiau AL, Lei HY, Tan TH, Ling P (2012) TBK1-associated protein in endolysosomes (TAPE)/CC2D1A is a key regulator linking RIG-I-like receptors to antiviral immunity. J Biol Chem 287:32216–32221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Childress JL, Acar M, Tao C, Halder G (2006) Lethal Giant discs, a novel C2-domain protein, restricts Notch activation during endocytosis. Curr Biol 16:1–6

    Article  CAS  Google Scholar 

  • Choy L, Hagenbeek TJ, Solon M, French D, Finkle D, Shelton A, Venook R, Brauer MJ, Siebel CW (2017) Constitutive NOTCH3 signaling promotes the growth of basal breast cancers. Cancer Res 77:1439–1452

    Article  CAS  PubMed  Google Scholar 

  • Collinet C, Stoöter M, Bradshaw CR, Samusik N, Rink JC, Kenski D, Habermann B, Buchholz F, Henschel R, Mueller MS, Nagel WE, Fava E, Kalaidzidis Y, Zerial M (2010) Systems survey of endocytosis by multiparametric image analysis. Nature 464:243–250

    Article  CAS  PubMed  Google Scholar 

  • Couturier L, Trylinski M, Mazouni K, Darnet L, Schweisguth F (2014) A fluorescent tagging approach in Drosophila reveals late endosomal trafficking of Notch and Sanpodo. J Cell Biol 207:351–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daskalaki A, Shalaby NA, Kux K, Tsoumpekos G, Tsibidis GD, Muskavitch MA, Delidakis C (2011) Distinct intracellular motifs of Delta mediate its ubiquitylation and activation by Mindbomb1 and Neuralized. J Cell Biol 195:1017–1031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deshar R, Cho EB, Yoon SK, Yoon JB (2016) CC2D1A and CC2D1B regulate degradation and signaling of EGFR and TLR4. Biochem Biophys Res Commun 480:280–287

    Article  CAS  PubMed  Google Scholar 

  • Drusenheimer N, Migdal B, Jäckel S, Tveriakhina L, Scheider K, Schulz K, Gröper J, Köhrer K, Klein T (2015) The mammalian Orthologs of Drosophila Lgd, CC2D1A and CC2D1B, function in the endocytic pathway, but their individual loss of function does not affect Notch signalling. PLoS Genet 11 (12):e1005749

    Google Scholar 

  • Fontana JR, Posakony JW (2009) Both inhibition and activation of notch signaling rely on a conserved neuralized-binding motif in bearded proteins and the Notch ligand delta. Dev Biol 333:373–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gallagher CM, Knoblich J (2006) The conserved c2 domain protein lethal (2) giant discs regulates protein trafficking in Drosophila. Dev Cell 11:641–653

    Article  CAS  PubMed  Google Scholar 

  • Geissler K, Zach O (2012) Pathways involved in Drosophila and human cancer development: the Notch, Hedgehog, Wingless, Runt, and Trithorax pathway. Ann Hematol 91:645–669

    Article  CAS  PubMed  Google Scholar 

  • Hadjighassem MR, Austin MC, Szewcyk B, Daigle M, Stockmeier CA, Albert PR (2009) Human Freud-2/CC2D1B: a novel repressor of postsynaptic serotonin-1A receptor expression. Biol Psychiatry 66:214–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huotari J, Helenius A (2011) Endosome maturation. EMBO J 30:3481–3500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hurley JH (2015) ESCRTs are everywhere. EMBO J 34:2398–2407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaekel R, Klein T (2006) The Drosophila Notch inhibitor and tumor suppressor gene lethal (2) giant discs encodes a conserved regulator of endosomal trafficking. Dev Cell 11:655–669

    Article  CAS  PubMed  Google Scholar 

  • Jekely G, Rorth P (2003) Hrs mediates downregulation of multiple signalling receptors in Drosophila. EMBO Rep 4:1164–1168

    Article  CAS  Google Scholar 

  • Klein T (2003) The tumour suppressor gene l(2)giant discs is required to restrict the activity of Notch to the dorsoventral boundary during Drosophila wing development. Dev Biol 255:313–333

    Article  CAS  PubMed  Google Scholar 

  • Kovall RA, Gebelein B, Sprinzak D, Kopan R (2017) The canonical Notch signalling pathway: structural and biochemical insights into shape, sugar, and force. Dev Cell 41:228–241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar S, Oien DB, Khurana A, Cliby W, Hartmann L, Chien J, Shridhar V (2019) Coiled-coil and C2 Domain-Containing Protein 1A (CC2D1A) promotes chemotherapy resistance in ovarian cancer. Front Oncol 9:986

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee JA, Beigneux A, Ahmad ST, Young SG, Gao F-B (2007) ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr Biol 17:1561–1567

    Article  CAS  PubMed  Google Scholar 

  • Manzini MC, Xiong L, Shaheen R, Tambunan DE, Di Costanzo S, Mitisalis V, Tischfield DJ, Cinquino A, Ghaziuddin M, Christian M, Jiang Q, Laurent S, Nanjiani ZA, Rasheed S, Hill RS, Lizarraga SB, Gleason D, Sabbagh D, Salih MA, Alkuraya FS, Walsh CA (2014) CC2D1A regulates human intellectual and social function as well as NF-κB signaling homeostasis. Cell Rep 8:647–655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S (2003) Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways. Oncogene 22:3307–3318

    Article  CAS  PubMed  Google Scholar 

  • Matsuno K, Ito M, Hori K, Miyashita F, Suzuki S, Kishi N, Artavanis-Tsakonas S, Okano H (2002) Involvement of a proline-rich motif and RING-H2 finger of Deltex in the regulation of Notch-signaling. Development 129:1049–1159

    Article  CAS  PubMed  Google Scholar 

  • McMillan BJ, Schnute B, Ohlenhard N, Zimmerman B, Miles L, Beglova N, Klein T, Blacklow SC (2015) A tail of two sites: structural basis for recognition of Notch ligands by Mind bomb E3 ligases. Mol Cell 57:912–924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McMillan BJ, Tibbe C, Jeon H, Drabek AA, Klein T, Blacklow SC (2016) Electrostatic interactions between elongated monomers drive Filamentation of Drosophila shrub, a metazoan ESCRT-III protein. Cell Rep 16:1211–1217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McMillan BJ, Tibbe C, Drabek AA, Seegar TCM, Blacklow SC, Klein T (2017) Structural basis for regulation of ESCRT-III complexes by Lgd. Cell Rep 19:1–8

    Article  CAS  Google Scholar 

  • Morawa K, Schneider M, Klein T (2015) Lgd regulates the activity of the BMP/Dpp signalling pathway during Drosophila oogenesis. Development 142:1325–1335

    Article  CAS  PubMed  Google Scholar 

  • Mukherjee A, Veraksa A, Bauer A, Rosse C, Camonis J, Artavanis-Tsakonas S (2005) Regulation of Notch signalling by non-visual ß-arrestin. Nat Cell Biol 7:1191–1201

    Article  PubMed  CAS  Google Scholar 

  • Nakamura A, Naito M, Tsuruo T, Fujita N (2008) Freud-1/Aki1, a novel PDK1-interacting protein, functions as a scaffold to activate the PDK1/Akt pathway in epidermal growth factor signaling. MCB 28:5996–6009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakamura A, Arai H, Fujita M (2009) Centrosomal Aki1 and cohesin function in separase-regulated centriole disengagement. JCB 187:607–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oaks AW, Zamarbide M, Tambunan DE, Santini E, Di Costanzo S, Pond HL, Johnson MW, Lin J, Gonzalez DM, Boehler JF, Wu GK, Klann E, Walsh CA, Manzini MC (2017) Cc2d1a loss of function disrupts functional and morphological development in forebrain neurons leading to cognitive and social deficits. Cereb Cortex 27:1670–1685

    Article  PubMed  Google Scholar 

  • Ohtsubo K, Yamada T, Zhao L, Jin TF, Takeuchi S, Mouri H, Yamashita K, Yasumoto K, Fujita N, Kitagawa H, Ohta T, Ikeda H, Yano S (2014) Expression of Akt kinase-interacting protein 1, a scaffold protein of the PI3K/PDK1/Akt pathway, in pancreatic cancer. Pancreas 43:1093–1100

    Article  CAS  PubMed  Google Scholar 

  • Ou X-M, Lemonde S, Jafar-Nejad H, Bown CD, Goto A, Rogaeva A, Albert PR (2003) Freud-1: a neuronal calcium-regulated repressor of the 5-HT1A receptor gene. J Neurosci 23:7415–7425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pasternak SH, Bagshaw RD, Guiral M, Zhang S, Ackerley CA, Pak BJ, Callahan JW, Mahuran DJ (2003) Presenilin-1, nicastrin, amyloid precursor protein, and gamma-secretase activity are co-localized in the lysosomal membrane. J Biol Chem (29):26687–26694

    Google Scholar 

  • Rogaeva A, Ou XM, Jafar-Nejad H, Lemonde S, Albert PR (2007) Differential repression by freud-1/CC2D1A at a polymorphic site in the dopamine-D2 receptor gene. J Biol Chem 282:20897–20905

    Article  CAS  PubMed  Google Scholar 

  • Schneider M, Troost T, Grawe F, Martinez-Arias A, Klein T (2012) Activation of Notch in lgd mutant cells requires the fusion of late endosomes with the lysosome. J Cell Sci 126:645–656

    Article  PubMed  CAS  Google Scholar 

  • Schnute B, Troost T, Klein T (2018) Endocytic trafficking of the Notch receptor. Adv Exp Med Biol 1066:99–122

    Article  CAS  PubMed  Google Scholar 

  • Scott CC, Gruenberg J (2010) Ion flux and the function of endosomes and lysosomes: pH is just the start. Bioassays 33:103–110

    Article  CAS  Google Scholar 

  • Shim J-H, Cxiao C, Hayden MS, Lee K-Y, Trombetta ES, Pypaert M, Nara A, Yoshimori T, Wilm B, Erdjument-Bromage H, Tempst P, Hogan BLM, Mellman I, Gosh S (2006) CHMP5 is essential for late endosome function and down-regulation of receptor signaling during mouse embryogenesis. JCB 172:1045–1056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimizu H, Woodcock SA, Wilkin MB, Trubenová B, Monk NA, Baron M (2014) Compensatory flux changes within an endocytic trafficking network maintain thermal robustness of Notch signaling. Cell (5):1160–1174

    Google Scholar 

  • Siebel C, Lendahl U (2017) Notch signaling in development, tissue homeostasis, and disease. Physiol Rev 97:1235–1294

    Article  CAS  PubMed  Google Scholar 

  • Steinbuck MP, Arakcheeva K, Winandy S (2018) Novel TCR-mediated mechanisms of Notch activation and signaling. J Immunol 200:997–1007

    Article  CAS  PubMed  Google Scholar 

  • Struhl G, Adachi A (2000) Requirements for Presenilin-dependent cleavage of Notch and other transmembrane proteins. Mol Cell 6:625–636

    Article  CAS  PubMed  Google Scholar 

  • Stuffers S, Wegner CS, Stenmark H, Brech A (2009) Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic 10:925–937

    Article  CAS  PubMed  Google Scholar 

  • Takebe N, Harris PJ, Warren RQ, Ivy SP (2011) Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol 8:97–106

    Article  CAS  PubMed  Google Scholar 

  • Tang S, Henne WM, Borbat PP, Buchkovich NJ, Freed JH, Mao Y, Fromme JC, EMR SD (2015) Structural basis for activation, assembly and membrane binding of ESCRT-III Snf7 filaments. elife 4

    Google Scholar 

  • Thompson BJ, Mathieu J, Sung HH, Loeser E, Rorth P, Cohen SM (2005) Tumor suppressor properties of the ESCRT-II complex component Vps25 in Drosophila. Dev Cell 9:711–720

    Article  CAS  PubMed  Google Scholar 

  • Troost T, Jaeckel S, Ohlenhard N, Klein T (2012) The tumour suppressor Lethal (2) giant discs is required for the function of the ESCRT-III component Shrub/CHMP4. JCS 125:763–776

    Article  CAS  Google Scholar 

  • Tsang HTH, Connell JW, Brown SE, Thompson A, Reid E, Sanderson CM (2006) A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex. Genomics 88:333–346

    Article  CAS  PubMed  Google Scholar 

  • Usami Y, Popov S, Weiss ER, Vriesema-Magnuson C, Calistri A, Göttlinger HG (2012) Regulation of CHMP4/ESCRT-III function in human immunodeficiency virus type 1 budding by CC2D1A. J Virol 86:3746–3756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vaccari T, Bilder D (2005) The Drosophila tumor suppressor vps25 prevents nonautonomous overproliferation by regulating notch trafficking. Dev Cell 9:687–698

    Article  CAS  PubMed  Google Scholar 

  • Vaccari T, Lu H, Kanwar R, Fortini M, Bilder D (2008) Endosomal entry regulates Notch receptor activation in Drosophila melanogaster. J Cell Biol 180:755–762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vaccari T, Rusten TE, Menut L, Nezis IP, Brech A, Stenmark H, Bilder D (2009) Comparative analysis of ESCRT-I, ESCRT-II and ESCRT-III function in Drosophila by efficient isolation of ESCRT mutants. J Cell Sci 122:2413–2423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vahid-Ansari F, Daigle M, Manzini MC, Tanaka KF, Hen R, Geddes SD, Béïque JC, James J, Merali Z, Albert PR (2017) Abrogated Freud-1/Cc2d1a repression of 5-HT1A autoreceptors induces fluoxetine-resistant anxiety/depression-like behavior. J Neurosci 37:11967–11978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ventimiglia LN, Cuesta-Geijo MA, Martinelli N, Caballe A, Macheboeuf P, Miguet N, Parnham IM, Olmos Y, Carlton JG, Weissenhorn W, Martin-Serrano J (2018) CC2D1B coordinates ESCRT-III activity during the mitotic reformation of the nuclear envelope. Dev Cell 47:547–563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vietri M, Radulovic M, Stenmark H (2020) The many functions of ESCRTs. Nat Rev Cell Biol 21:25–42

    Article  CAS  Google Scholar 

  • Wagner KU, Krempler A, Qi Y, Park K, Henry MD, Triplett AA, Riedlinger G, Rucker IEB, Hennighausen L (2003) Tsg101 is essential for cell growth, proliferation, and cell survival of embryonic and adult tissues. Mol Biol Cell 23:150–162

    Article  CAS  Google Scholar 

  • Weinmaster G, Fischer JA (2011) Notch ligand ubiquitylation: what is it good for? Dev Cell 21:134–144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilkin M, Tongngok P, Gensch N, Clemence S, Motoki M, Yamada K, Hori K, Taniguchi-Kanai M, Franklin E, Matsuno K, Baron M (2008) Drosophila HOPS and AP-3 complex genes are required for a Deltex-regulated activation of notch in the endosomal trafficking pathway. Dev Cell 15:762–772

    Article  CAS  PubMed  Google Scholar 

  • Windler SL, Bilder D (2010) Endocytic internalization routes required for Delta/Notch signaling. Curr Biol 20:538–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamada T, Takeuchi S, Fujita N, Nakamura A, Wang W, Li Q, Oda M, Mitsudomi T, Yatabe Y, Sekido Y, Yoshida J, Higashiyama M, Noguchi M, Uehara H, Nishioka Y, Sone S, Yano S (2013) Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR-activating and gatekeeper mutations. Oncogene 32:4427–4435

    Article  CAS  PubMed  Google Scholar 

  • Zamarbide M, Oaks AW, Pond HL, Adelman JS, Manzini MC (2018) Loss of the intellectual disability and autism gene Cc2d1a and its homolog Cc2d1b differentially affect spatial memory, anxiety, and hyperactivity. Front Genet 9:65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhao M, Li X-D, Chen Z (2010) CC2D!A, a DM14 and C2 domain protein, activates NF-kB through the canonical pathway. JBC 285:24372–24380

    Article  CAS  Google Scholar 

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Acknowledgements

Work in the Klein lab is supported by the Deutsche Forschungsgemeinschaft (DFG) through Teilprojekt B01 of the CRC 1208 “Identity and Dynamics of Membrane Systems-from Molecules to Cellular Functions” and Sachbeihilfe KL-1028/5-2. We apologise to every researcher whose publications are not cited due to restrictions in space. The Reiff lab is supported by the Deutsche Forschungsgemeinschaft (DFG) by Sachbeihilfe RE-3453/3-1 and the Wilhelm Sander-Stiftung 2018.145.1.

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Authors and Affiliations

  1. Institut fuer Genetik, Heinrich-Heine-Universitaet Duesseldorf, Duesseldorf, Germany

    Tobias Reiff, Miriam Baeumers, Christine Tibbe & Thomas Klein

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  1. Tobias Reiff
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  2. Miriam Baeumers
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  3. Christine Tibbe
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  4. Thomas Klein
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Correspondence to Thomas Klein .

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  1. Department of Dermatology, Saarland University Medical Center, Homburg, Saarland, Germany

    Jörg Reichrath

  2. Department of Dermatology, Saarland University Medical Center, Homburg, Saarland, Germany

    Sandra Reichrath

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Reiff, T., Baeumers, M., Tibbe, C., Klein, T. (2021). Unravelling of Hidden Secrets: The Tumour Suppressor Lethal (2) Giant Discs (Lgd)/CC2D1, Notch Signalling and Cancer. In: Reichrath, J., Reichrath, S. (eds) Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine and Biology, vol 1287. Springer, Cham. https://doi.org/10.1007/978-3-030-55031-8_3

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