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journal article·2026-04Open access

Strawberry Notch 1 Acts as a Transcriptional Regulator Driving Oncogenic Programs in Liver Carcinogenesis

Sarah Fritzsche, Raisatun Nisa Sugiyanto, Kira Gür, Alina Krumme, Maxime Le Marois, Angelika Fraas, Aslihan Inal, Mario Huerta, Vanessa Henriques, Eva Eiteneuer, Thomas Albrecht, Alphonse Charbel, Michael T. Dill, Carsten Sticht, Carolina De La Torre, Stefan Pusch, Arianeb Mehrabi, Kai Breuhahn, Junfang Ji, Peter Schirmacher, Benjamin Goeppert, Stephanie Roessler

Advanced Science· Volume 13· Issue 20
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Source abstract

Abstract

ABSTRACT Aberrant Notch signaling has been identified as a key driver of cancer development. Genetic studies in Drosophila showed that the knockout of strawberry notch ( sno ) mimics the loss of notch . Here, we found that Strawberry Notch 1 (SBNO1) is upregulated in several cancer entities and elucidated the role of SBNO1 in liver cancer development. In hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), SBNO1 protein was significantly increased and localized to the nucleus suggesting its involvement in gene regulation. SBNO1‐inhibition reduced cell viability, colony formation and migration and induced distinct expression patterns in HCC and CCA cell lines. However, BioID revealed that SBNO1 similarly modulates gene regulation in HCC and CCA by binding to general transcription factors TAF4 and TAF3. Deletion of Sbno1 in murine liver cancer cells Hep55.1C reduced tumor growth in vivo. In addition, inhibition of Sbno1 significantly reduced liver tumor development in three different mouse models of HCC and CCA. Furthermore, Sbno1 ‐deletion reduced biliary differentiation and angiogenesis in the tumor margin, underscoring the necessity of Sbno1 in Notch‐driven CCA formation. Thus, we identified SBNO1 as a transcriptional regulator required for liver cancer development and progression.
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Research context

OpenAlex topics: Developmental Biology and Gene Regulation · Wnt/β-catenin signaling in development and cancer · Hippo pathway signaling and YAP/TAZ

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Pathology, University Hospital Heidelberg Medical Faculty Heidelberg University Heidelberg Germany

Laboratory of Macromolecular Engineering Department of Pharmaceutical Chemistry Faculty of Pharmacy Universitas Gadjah Mada Yogyakarta Indonesia

Department of Gastroenterology Hepatology Infectious Diseases and Intoxications Heidelberg University Hospital Heidelberg Germany

German Cancer Research Center (DKFZ) Heidelberg Experimental Hepatology Inflammation and Cancer Heidelberg Germany

Liver Cancer Center Heidelberg (LCCH) Heidelberg Germany

NGS Core Facility Medical Faculty Mannheim Heidelberg University Mannheim Germany

Department of Neuropathology University Hospital Heidelberg Heidelberg Germany

Clinical Cooperation Unit Neuropathology German Cancer Research Center Heidelberg Germany

Department of General Visceral and Transplantation Surgery University Hospital Heidelberg Heidelberg Germany

The MOE Key Laboratory of Biosystems Homeostasis & Protection Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology and Innovation Center for Cell Signaling Network Life Sciences Institute Zhejiang University Hangzhou China

Institute of Pathology Hospital RKH Kliniken Ludwigsburg Ludwigsburg Germany

Institute of Tissue Medicine and Pathology University of Bern Bern Switzerland

German Cancer Consortium (DKTK), DKFZ Core Center Heidelberg Germany

Funding

Deutsche Krebshilfe · Deutsche Forschungsgemeinschaft

References (76)

Show source-provided references
1. 10.1016/j.ccr.2014.02.01810.1016/j.ccr.2014.02.018 ↗
2. 10.1053/j.gastro.2012.09.00210.1053/j.gastro.2012.09.002 ↗
3. 10.1053/j.gastro.2013.02.00910.1053/j.gastro.2013.02.009 ↗
4. 10.1172/JCI6321210.1172/JCI63212 ↗
5. 10.1084/jem.2011019810.1084/jem.20110198 ↗
6. 10.3322/caac.2166010.3322/caac.21660 ↗
7. 10.1016/j.jhep.2022.05.03710.1016/j.jhep.2022.05.037 ↗
8. 10.1038/s41575‐020‐0310‐z10.1038/s41575‐020‐0310‐z ↗
9. 10.1002/hep.3111010.1002/hep.31110 ↗
10. 10.1038/nrdp.2016.1810.1038/nrdp.2016.18 ↗
11. 10.1016/j.jhep.2017.05.01410.1016/j.jhep.2017.05.014 ↗
12. 10.1016/j.jhep.2022.08.02110.1016/j.jhep.2022.08.021 ↗
13. 10.1016/j.jhepr.2020.10013410.1016/j.jhepr.2020.100134 ↗
14. 10.1038/nrclinonc.2017.15710.1038/nrclinonc.2017.157 ↗
15. 10.1038/s41388‐020‐1198‐310.1038/s41388‐020‐1198‐3 ↗
16. 10.1038/s41418‐020‐0505‐410.1038/s41418‐020‐0505‐4 ↗
17. 10.1097/HEP.000000000000032210.1097/HEP.0000000000000322 ↗
18. 10.1038/nrm.2016.9410.1038/nrm.2016.94 ↗
19. 10.1242/dev.119.2.37710.1242/dev.119.2.377 ↗
20. 10.1101/gad.11.10.134110.1101/gad.11.10.1341 ↗
21. 10.1053/j.gastro.2011.12.00510.1053/j.gastro.2011.12.005 ↗
22. 10.1016/j.jhep.2020.03.00810.1016/j.jhep.2020.03.008 ↗
23. 10.1002/mc.294006021010.1002/mc.2940060210 ↗
24. 10.1002/hep.2848710.1002/hep.28487 ↗
25. 10.1002/hep.2473610.1002/hep.24736 ↗
26. 10.1016/j.ajpath.2017.07.02210.1016/j.ajpath.2017.07.022 ↗
27. 10.1136/gutjnl‐2012‐30435110.1136/gutjnl‐2012‐304351 ↗
28. 10.1083/jcb.20111209810.1083/jcb.201112098 ↗
29. 10.1038/ncomms1106310.1038/ncomms11063 ↗
30. 10.1016/j.bcp.2021.11467210.1016/j.bcp.2021.114672 ↗
31. 10.1186/s12929‐017‐0374‐410.1186/s12929‐017‐0374‐4 ↗
32. 10.1074/jbc.M112.38086510.1074/jbc.M112.380865 ↗
33. 10.1038/emboj.2008.2510.1038/emboj.2008.25 ↗
34. 10.1126/sciadv.add496910.1126/sciadv.add4969 ↗
35. 10.1038/s41594‐023‐01026‐310.1038/s41594‐023‐01026‐3 ↗
36. 10.1038/s41420‐022‐01201‐310.1038/s41420‐022‐01201‐3 ↗
37. 10.1002/hep.2459510.1002/hep.24595 ↗
38. 10.1016/j.jhep.2023.03.00310.1016/j.jhep.2023.03.003 ↗
39. 10.1016/j.jhep.2022.11.00510.1016/j.jhep.2022.11.005 ↗
40. 10.1056/EVIDoa220001510.1056/EVIDoa2200015 ↗
41. 10.1016/j.cell.2023.07.02610.1016/j.cell.2023.07.026 ↗
42. 10.1371/journal.pone.021951710.1371/journal.pone.0219517 ↗
43. 10.1016/j.ajpath.2013.12.00210.1016/j.ajpath.2013.12.002 ↗
44. 10.1158/0008‐5472.CAN‐14‐052710.1158/0008‐5472.CAN‐14‐0527 ↗
45. 10.1016/j.ccr.2013.04.01910.1016/j.ccr.2013.04.019 ↗
46. 10.1038/s41573‐020‐00091‐310.1038/s41573‐020‐00091‐3 ↗
47. 10.1016/s0092‐8674(02)00875‐910.1016/s0092‐8674(02)00875‐9 ↗
48. 10.4103/aja.aja_65_1810.4103/aja.aja_65_18 ↗
49. 10.1038/srep4613510.1038/srep46135 ↗
50. 10.1002/glia.2284110.1002/glia.22841 ↗
51. 10.1182/blood.202201849410.1182/blood.2022018494 ↗
52. 10.1128/MCB.24.23.10223‐10235.200410.1128/MCB.24.23.10223‐10235.2004 ↗
53. 10.1101/gad.7.4.67110.1101/gad.7.4.671 ↗
54. 10.1038/378203a010.1038/378203a0 ↗
55. 10.1186/s12943‐024‐02024‐910.1186/s12943‐024‐02024‐9 ↗
56. 10.1158/1535‐7163.MCT‐23‐074710.1158/1535‐7163.MCT‐23‐0747 ↗
57. Nakanuma Y. · 2019 · 254
58. Brierley J. D. · 2017
59. 10.1136/jcp‐2024‐20942910.1136/jcp‐2024‐209429 ↗
60. 10.1038/s41598‐017‐17204‐510.1038/s41598‐017‐17204‐5 ↗
61. 10.1002/ijc.2511810.1002/ijc.25118 ↗
62. 10.1002/hep.2868410.1002/hep.28684 ↗
63. 10.1038/nmeth.304710.1038/nmeth.3047 ↗
64. 10.1111/j.1755‐148X.2009.00545.x10.1111/j.1755‐148X.2009.00545.x ↗
65. 10.1126/science.123114310.1126/science.1231143 ↗
66. 10.1053/j.gastro.2010.12.00610.1053/j.gastro.2010.12.006 ↗
67. 10.1093/nar/gni17910.1093/nar/gni179 ↗
68. 10.1186/s12859‐016‐1241‐010.1186/s12859‐016‐1241‐0 ↗
69. 10.1038/nbt.351910.1038/nbt.3519 ↗
70. 10.1093/nar/gkv00710.1093/nar/gkv007 ↗
71. 10.1093/bioinformatics/btaa17110.1093/bioinformatics/btaa171 ↗
72. 10.1093/bioinformatics/bts63510.1093/bioinformatics/bts635 ↗
73. 10.1093/bioinformatics/btt65610.1093/bioinformatics/btt656 ↗
74. 10.1038/nmeth.192310.1038/nmeth.1923 ↗
75. 10.1101/08226310.1101/082263 ↗
76. 10.1093/bioinformatics/btv14510.1093/bioinformatics/btv145 ↗