B03

The roles of Wnt signaling in genome stability

Funding period: 2017-2029

Project B03

Project Leaders

Prof. Dr. Sergio P. Acebrón

 Project Leader B03

Prof. Dr. Holger Bastians

 Project Leader B03

Abstract

We found that Wnt signaling regulates DNA replication stress-induced mitotic errors and genome instability in embryonic and pluripotent stem cells as well as in human somatic and colorectal cancer cells. We aim to determine how Wnt10b ligands shape genomic evolution in colorectal cancer by integrating molecular analyses of DNA replication and mitosis, live cell imaging, as well as INDUCE-seq and scG&T-seq analyses in cell lines and patient-derived organoids. We will also investigate whether and how Wnt10b activity can modulate the response to chemotherapies targeting replication stress in colorectal cancer.

Project-related Publications

The interplay between Wnt and mTOR signaling modulates ciliogenesis in human retinal epithelial cells.

Yuan C, Neuner A, Streubel J, Bhanushali A, Simons M, Acebrón SP, Pereira G. PLoS Biol. 2025 Sep 2;23(9):e3003369. doi: 10.1371/journal.pbio.3003369. eCollection 2025 Sep. PMID: 40892854

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Wnt10b signaling regulates replication stress-induced chromosomal instability in human cancer

Haas A, Wenz F, Hattemer J, Wesslowski J, Davidson G, Voloshanenko O, Boutros M, Acebron SP, Bastians H. Life Sci Alliance. 2025 Aug 22;8(11):e202503295. doi: 10.26508/lsa.202503295. Print 2025 Nov. PMID: 40846632

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A novel biosensor for the spatiotemporal analysis of STING activation during innate immune responses to dsDNA

Smarduch S, Moreno-Velasquez SD, Ilic D, Dadsena S, Morant R, Ciprinidis A, Pereira G, Binder M, García-Sáez AJ, Acebrón SP. EMBO J. 2025 Apr;44(7):2157-2182.

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Activation of Wnt/β-catenin signaling is critical for the tumorigenesis of choroid plexus

Ho KH, Trapp M, Guida C, Ivanova EL, De Jaime-Soguero A, Jabali A, Thomas C, Salasova A, Bernatík O, Salio C, Horschitz S, Hasselblatt M, Sassoè-Pognetto M, Čajánek L, Ishikawa H, Schroten H, Schwerk C, Acebrón SP, Angel P, Koch P, Patrizi A. Neuro Oncol. 2025 Jan 12;27(1):106-122

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Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress

de Jaime-Soguero A, Hattemer J, Bufe A, Haas A, van den Berg J, van Batenburg V, Das B, di Marco B, Androulaki S, Böhly N, Landry JJM, Schoell B, Rosa VS, Villacorta L, Baskan Y, Trapp M, Benes V, Chabes A, Shahbazi M, Jauch A, Engel U, Patrizi A, Sotillo R, van Oudenaarden A, Bageritz J, Alfonso J, Bastians H, Acebrón SP. Nat Commun. 2024 Aug 28;15(1):7404. doi: 10.1038/s41467-024-51821-9. PMID: 39191776

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DEAD box RNA helicases are pervasive protein kinase interactors and activators

Hirth A, Fatti E, Netz E, Acebron SP, Papageorgiou D, Švorinić A, Cruciat CM, Karaulanov E, Gopanenko A, Zhu T, Sinning I, Krijgsveld J, Kohlbacher O, Niehrs C. Genome Res. 2024 Jul 23;34(6):952-966. doi: 10.1101/gr.278264.123. PMID: 38986579

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DEAD box RNA helicases act as nucleotide exchange factors for casein kinase 2

Fatti E, Hirth A, Švorinić A, Günther M, Stier G, Cruciat CM, Acebrón SP, Papageorgiou D, Sinning I, Krijgsveld J, Höfer T, Niehrs C. Sci Signal. 2023 Apr 25;16(782):eabp8923. doi: 10.1126/scisignal.abp8923. Epub 2023 Apr 25. PMID: 37098120

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Wnt signalling in cell division: from mechanisms to tissue engineering

Habib SJ, Acebrón SP. Trends Cell Biol. 2022 Jun 15:S0962-8924(22)00137-4. doi: 10.1016/j.tcb.2022.05.006. Online ahead of print. PMID: 35717422

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Mitotic WNT: aligning chromosomes through KIF2A

Bufe A, Acebrón SP. Mol Cell Oncol. 2021 Dec 6;8(6):2011564. doi: 10.1080/23723556.2021.2011564. eCollection 2021. PMID: 35419471

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Wnt signaling recruits KIF2A to the spindle to ensure chromosome congression and alignment during mitosis

Bufe A, García Del Arco A, Hennecke M, de Jaime-Soguero A, Ostermaier M, Lin YC, Ciprianidis A, Hattemer J, Engel U, Beli P, Bastians H, Acebrón SP. Proc Natl Acad Sci U S A. 2021 Aug 24; 118(34):e2108145118. doi:10.1073/pnas.2108145118. PMID: 34417301

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USP42 protects ZNRF3/RNF43 from R‐spondin‐dependent clearance and inhibits Wnt signalling

Giebel N, de Jaime-Soguero A, García Del Arco A, Landry JJM, Tietje M, Villacorta L, Benes V, Fernández-Sáiz V, Acebrón SP. EMBO Rep. 2021 Mar 30:e51415. doi: 10.15252/embr.202051415. Online ahead of print.
PMID: 33786993

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Wnt10b GSK3β dependent Wnt/STOP signaling prevents aneuploidy in human somatic cells

Lin YC, Haas A, Bufe A, Parbin S, Hennecke M, Voloshanenko O, Gross J, Boutros M, Acebron SP, Bastians H. Life Sci Alliance. 2020 Nov 30;4(1):e202000855. Print 2021 Jan.
PMID: 33257473

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The p53/p73 – p21CIP1 tumor suppressor axis guards against chromosomal instability by restraining CDK1 in human cancer cells

Schmidt AK, Pudelko K, Boekenkamp JE, Berger K, Kschischo M, Bastians H. Oncogene. 2021 Jan;40(2):436-451. doi: 10.1038/s41388-020-01524-4. Epub 2020 Nov 9. PMID: 33168930

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Mild replication stress causes aneuploidy by deregulating microtubule dynamics in mitosis

Böhly N, Kistner M, Bastians H. Cell Cycle. 2019 Oct;18(20):2770-2783. doi: 10.1080/15384101.2019.1658477. Epub 2019 Aug 25. PMID: 31448675

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A Cell-Based Assay for Mitotic Spindle Orientation

Glaubke E, Bastians H. Methods Mol Biol. 2018;1787:67-75. doi: 10.1007/978-1-4939-7847-2_5. PMID:29736710

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Parkinson associated receptor GPR37 is an ER chaperone for LRP6

Berger BS, Acebron SP, Herbst J, Koch S, Niehrs C. EMBO Rep. 2017 May;18(5):712-725. doi: 10.15252/embr.201643585. Epub 2017 Mar 24. PMID: 28341812

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Posttranscriptional Wnt signaling governs epididymal sperm maturation

Koch S, Acebron SP, Herbst J, Hatiboglu G, Niehrs C. Cell. 2015 Nov 19;163(5):1225-1236. doi: 10.1016/j.cell.2015.10.029. PMID: 26590424

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Maternal Wnt/STOP signaling promotes cell division during early Xenopus embryogenesis

Huang YL, Anvarian Z, Döderlein G, Acebron SP, Niehrs C. Proc Natl Acad Sci U S A. 2015 May 5;112(18):5732-7. doi: 10.1073/pnas.1423533112. Epub 2015 Apr 21. PMID: 25901317

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Wnt-mediated protein stabilization ensures proper mitotic microtubule assembly and chromosome segregation

Stolz A, Neufeld K, Ertych N, Bastians H. EMBO Rep. 2015 Apr;16(4):490-9. doi: 10.15252/embr.201439410. Epub 2015 Feb 5. PMID: 25656539

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Increased microtubule assembly rates influence chromosomal instability in colorectal cancer cells.

Ertych N, Stolz A, Stenzinger A, Weichert W, Kaulfuß S, Burfeind P, Aigner A, Wordeman L, Bastians H. Nat Cell Biol. 2014 Aug;16(8):779-91. doi: 10.1038/ncb2994. Epub 2014 Jun 29. PMID: 24976383

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Mitotic wnt signaling promotes protein stabilization and regulates cell size

Acebron SP, Karaulanov E, Berger BS, Huang YL, Niehrs C. Mol Cell. 2014 May 22;54(4):663-74. doi: 10.1016/j.molcel.2014.04.014. Epub 2014 May 15. PMID: 24837680

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