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Cantù, Claudio, ProfessorORCID iD iconorcid.org/0000-0003-1547-5415
Publications (10 of 12) Show all publications
Nordin, A., Pagella, P., Zambanini, G. & Cantù, C. (2024). Exhaustive identification of genome-wide binding events of transcriptional regulators. Nucleic Acids Research, 52(7), Article ID e40.
Open this publication in new window or tab >>Exhaustive identification of genome-wide binding events of transcriptional regulators
2024 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 52, no 7, article id e40Article in journal (Refereed) Published
Abstract [en]

Genome-wide binding assays aspire to map the complete binding pattern of gene regulators. Common practice relies on replication-duplicates or triplicates-and high stringency statistics to favor false negatives over false positives. Here we show that duplicates and triplicates of CUT&RUN are not sufficient to discover the entire activity of transcriptional regulators. We introduce ICEBERG (Increased Capture of Enrichment By Exhaustive Replicate aGgregation), a pipeline that harnesses large numbers of CUT&RUN replicates to discover the full set of binding events and chart the line between false positives and false negatives. We employed ICEBERG to map the full set of H3K4me3-marked regions, the targets of the co-factor beta-catenin, and those of the transcription factor TBX3, in human colorectal cancer cells. The ICEBERG datasets allow benchmarking of individual replicates, comparing the performance of peak calling and replication approaches, and expose the arbitrary nature of strategies to identify reproducible peaks. Instead of a static view of genomic targets, ICEBERG establishes a spectrum of detection probabilities across the genome for a given factor, underlying the intrinsic dynamicity of its mechanism of action, and permitting to distinguish frequent from rare regulation events. Finally, ICEBERG discovered instances, undetectable with other approaches, that underlie novel mechanisms of colorectal cancer progression. Graphical Abstract

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2024
National Category
Genetics and Genomics
Identifiers
urn:nbn:se:liu:diva-202261 (URN)10.1093/nar/gkae180 (DOI)001186621600001 ()38499482 (PubMedID)2-s2.0-85191601570 (Scopus ID)
Note

Funding Agencies|Cancerfonden [CAN 2018/542, 21 1572 Pj]; Swedish Research Council, Vetenskapsradet [2021-03075, 202301898]; Linkoping University and LiU-Cancer, and Additional Ventures (USA) [SVRF2021-1048003]; Knut and Alice Wallenberg Foundation; National Supercomputer Centre (NSC) - Linkoping University; Library of the Linkoping University

Available from: 2024-04-09 Created: 2024-04-09 Last updated: 2025-02-18Bibliographically approved
Pizzolato, G., Moparthi, L., Pagella, P., Cantù, C., D´arcy, P. & Koch, S. (2024). The tumour suppressor p53 is a negative regulator of the carcinoma-associated transcription factor FOXQ1. Journal of Biological Chemistry, 300(4), Article ID 107126.
Open this publication in new window or tab >>The tumour suppressor p53 is a negative regulator of the carcinoma-associated transcription factor FOXQ1
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2024 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 300, no 4, article id 107126Article in journal (Refereed) Published
Abstract [en]

The forkhead box family transcription factor FOXQ1 is highly induced in several types of carcinomas, where it promotes epithelial-to-mesenchymal transition and tumour metastasis. The molecular mechanisms that lead to FOXQ1 deregulation in cancer are incompletely understood. Here, we used CRISPR/Cas9-based genomic locus proteomics (GLoPro) and promoter reporter constructs to discover transcriptional regulators of FOXQ1, and identified the tumour suppressor p53 as a negative regulator of FOXQ1 expression. ChIP-qPCR as well as complementary gain and loss-of-function assays in model cell lines indicated that p53 binds close to the transcription start site of the FOXQ1 promoter, and that it suppresses FOXQ1 expression in various cell types. Consistently, pharmacological activation of p53 using nutlin-3 or doxorubicin reduced FOXQ1 mRNA and protein levels in cancer cell lines harboring wild-type p53. Finally, we observed that p53 mutations are associated with increased FOXQ1 expression in human cancers. Altogether, these results suggest that loss of p53 function - a hallmark feature of many types of cancer - de-represses FOXQ1, which in turn promotes tumour progression.

Place, publisher, year, edition, pages
Elsevier, 2024
National Category
Cell Biology
Identifiers
urn:nbn:se:liu:diva-201384 (URN)10.1016/j.jbc.2024.107126 (DOI)001345336700001 ()38432629 (PubMedID)
Note

Funding Agencies|Veten-skapsrdet [23 2635, 21 1572 Pj];  [2021-03075]

Available from: 2024-03-06 Created: 2024-03-06 Last updated: 2025-01-31Bibliographically approved
Diener, J., Baggiolini, A., Pernebrink, M., Dalcher, D., Lerra, L., Cheng, P. F., . . . Sommer, L. (2021). Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4. Nature Communications, 12(1), Article ID 5056.
Open this publication in new window or tab >>Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4
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2021 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 12, no 1, article id 5056Article in journal (Refereed) Published
Abstract [en]

Melanoma cells rely on developmental programs during tumor initiation and progression. Here we show that the embryonic stem cell (ESC) factor Sall4 is re-expressed in the Tyr::Nras(Q61K); Cdkn2a(-/-) melanoma model and that its expression is necessary for primary melanoma formation. Surprisingly, while Sall4 loss prevents tumor formation, it promotes micrometastases to distant organs in this melanoma-prone mouse model. Transcriptional profiling and in vitro assays using human melanoma cells demonstrate that SALL4 loss induces a phenotype switch and the acquisition of an invasive phenotype. We show that SALL4 negatively regulates invasiveness through interaction with the histone deacetylase (HDAC) 2 and direct co-binding to a set of invasiveness genes. Consequently, SALL4 knock down, as well as HDAC inhibition, promote the expression of an invasive signature, while inhibition of histone acetylation partially reverts the invasiveness program induced by SALL4 loss. Thus, SALL4 appears to regulate phenotype switching in melanoma through an HDAC2-mediated mechanism. Melanoma cells can switch between proliferative and invasive phenotypes. Here the authors show that the embryonic stem cell factor Sall4 is a negative regulator of melanoma phenotype switching where its loss leads to the acquisition of an invasive phenotype, due to derepression of invasiveness genes.

Place, publisher, year, edition, pages
Nature Portfolio, 2021
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-178744 (URN)10.1038/s41467-021-25326-8 (DOI)000687171500004 ()34417458 (PubMedID)
Note

Funding Agencies|Functional Genomics Center Zurich (FGCZ) [p2155, p2419]; University of Zurich (University Priority Research Program (URPP) Translational Cancer Research); Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission [31003A_169859, 310030_192075]; Swiss Cancer Research foundation [KFS-4570-08-2018]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; CancerfondenSwedish Cancer Society [CAN 2018/542]; Candoc Forschungskredit [FK-19-026]

Available from: 2021-08-30 Created: 2021-08-30 Last updated: 2023-03-28
Pagin, M., Pernebrink, M., Pitasi, M., Malighetti, F., Ngan, C.-Y., Ottolenghi, S., . . . Nicolis, S. K. (2021). FOS Rescues Neuronal Differentiation of Sox2-Deleted Neural Stem Cells by Genome-Wide Regulation of Common SOX2 and AP1(FOS-JUN) Target Genes. Cells, 10(7), Article ID 1757.
Open this publication in new window or tab >>FOS Rescues Neuronal Differentiation of Sox2-Deleted Neural Stem Cells by Genome-Wide Regulation of Common SOX2 and AP1(FOS-JUN) Target Genes
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2021 (English)In: Cells, E-ISSN 2073-4409, Vol. 10, no 7, article id 1757Article in journal (Refereed) Published
Abstract [en]

The transcription factor SOX2 is important for brain development and for neural stem cells (NSC) maintenance. Sox2-deleted (Sox2-del) NSC from neonatal mouse brain are lost after few passages in culture. Two highly expressed genes, Fos and Socs3, are strongly downregulated in Sox2-del NSC; we previously showed that Fos or Socs3 overexpression by lentiviral transduction fully rescues NSCs long-term maintenance in culture. Sox2-del NSC are severely defective in neuronal production when induced to differentiate. NSC rescued by Sox2 reintroduction correctly differentiate into neurons. Similarly, Fos transduction rescues normal or even increased numbers of immature neurons expressing beta-tubulinIII, but not more differentiated markers (MAP2). Additionally, many cells with both beta-tubulinIII and GFAP expression appear, indicating that FOS stimulates the initial differentiation of a "mixed" neuronal/glial progenitor. The unexpected rescue by FOS suggested that FOS, a SOX2 transcriptional target, might act on neuronal genes, together with SOX2. CUT&RUN analysis to detect genome-wide binding of SOX2, FOS, and JUN (the AP1 complex) revealed that a high proportion of genes expressed in NSC are bound by both SOX2 and AP1. Downregulated genes in Sox2-del NSC are highly enriched in genes that are also expressed in neurons, and a high proportion of the "neuronal" genes are bound by both SOX2 and AP1.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
neural stem cells; neurogenesis; gliogenesis; CUT&RUN; transcription factors; chromatin; Sox2; Fos; Socs3
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-178451 (URN)10.3390/cells10071757 (DOI)000676781300001 ()34359927 (PubMedID)
Note

Funding Agencies|Fondo di Ateneo Quota Competitiva (2021); Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; CancerfondenSwedish Cancer Society [CAN 2018/542]

Available from: 2021-08-26 Created: 2021-08-26 Last updated: 2022-05-24
Buechel, D., Sugiyama, N., Rubinstein, N., Saxena, M., Kalathur, R. K. R., Luond, F., . . . Christofori, G. (2021). Parsing beta-catenins cell adhesion and Wnt signaling functions in malignant mammary tumor progression. Proceedings of the National Academy of Sciences of the United States of America, 118(34), Article ID e2020227118.
Open this publication in new window or tab >>Parsing beta-catenins cell adhesion and Wnt signaling functions in malignant mammary tumor progression
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2021 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 118, no 34, article id e2020227118Article in journal (Refereed) Published
Abstract [en]

During malignant progression, epithelial cancer cells dissolve their cell-cell adhesion and gain invasive features. By virtue of its dual function, beta-catenin contributes to cadherin-mediated cell-cell adhesion, and it determines the transcriptional output of Wnt signaling: via its N terminus, it recruits the signaling coactivators Bd9 and Pygo-pus, and via the C terminus, it interacts with the general transcriptional machinery. This duality confounds the simple loss-of-function analysis of Wnt signaling in cancer progression. In many cancer types including breast cancer, the functional contribution of beta-catenins transcriptional activities, as compared to its adhesion functions, to tumor progression has remained elusive. Employing the mouse mammary tumor virus (MMTV)-PyMT mouse model of metastatic breast cancer, we compared the complete elimination of beta-catenin with the specific ablation of its signaling outputs in mammary tumor cells. Notably, the complete lack of beta-catenin resulted in massive apoptosis of mammary tumor cells. In contrast, the loss of beta-catenins transcriptional activity resulted in a reduction of primary tumor growth, tumor invasion, and metastasis formation in vivo. These phenotypic changes were reflected by stalled cell cycle progression and diminished epithelial-mesenchymal transition (EMT) and cell migration of breast cancer cells in vitro. Transcriptome analysis revealed subsets of genes which were specifically regulated by beta-catenins transcriptional activities upon stimulation with Wnt3a or during TGF-beta-induced EMT. Our results uncouple the signaling from the adhesion function of beta-catenin and underline the importance of Wnt/beta-catenin-dependent transcription in malignant tumor progression of breast cancer.

Place, publisher, year, edition, pages
NATL ACAD SCIENCES, 2021
Keywords
beta-catenin; breast cancer; cell adhesion; metastasis; Wnt signaling
National Category
Cell Biology
Identifiers
urn:nbn:se:liu:diva-178945 (URN)10.1073/pnas.2020227118 (DOI)000689728100018 ()34408016 (PubMedID)
Note

Funding Agencies|Swiss NSFSwiss National Science Foundation (SNSF) [310030B_163471, 310030B_173331]; Swiss NSF Sinergia Grant; Swiss Cancer League [KFS-3479-08-2014]; Krebsliga Beider Basel [03-2013]

Available from: 2021-09-06 Created: 2021-09-06 Last updated: 2022-05-24
Pagin, M., Pernebrink, M., Giubbolini, S., Barone, C., Sambruni, G., Zhu, Y., . . . Nicolis, S. K. (2021). Sox2 controls neural stem cell self-renewal through a Fos-centered gene regulatory network. Stem Cells, 39(8), 1107-1119
Open this publication in new window or tab >>Sox2 controls neural stem cell self-renewal through a Fos-centered gene regulatory network
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2021 (English)In: Stem Cells, ISSN 1066-5099, E-ISSN 1549-4918, Vol. 39, no 8, p. 1107-1119Article in journal (Refereed) Published
Abstract [en]

The Sox2 transcription factor is necessary for the long-term self-renewal of neural stem cells (NSCs). Its mechanism of action is still poorly defined. To identify molecules regulated by Sox2, and acting in mouse NSC maintenance, we transduced, into Sox2-deleted NSC, genes whose expression is strongly downregulated following Sox2 loss (Fos, Jun, Egr2), individually or in combination. Fos alone rescued long-term proliferation, as shown by in vitro cell growth and clonal analysis. Furthermore, pharmacological inhibition by T-5224 of FOS/JUN AP1 complex binding to its targets decreased cell proliferation and expression of the putative target Suppressor of cytokine signaling 3 (Socs3). Additionally, Fos requirement for efficient long-term proliferation was demonstrated by the reduction of NSC clones capable of long-term expansion following CRISPR/Cas9-mediated Fos inactivation. Previous work showed that the Socs3 gene is strongly downregulated following Sox2 deletion, and its re-expression by lentiviral transduction rescues long-term NSC proliferation. Fos appears to be an upstream regulator of Socs3, possibly together with Jun and Egr2; indeed, Sox2 re-expression in Sox2-deleted NSC progressively activates both Fos and Socs3 expression; in turn, Fos transduction activates Socs3 expression. Based on available SOX2 ChIPseq and ChIA-PET data, we propose a model whereby Sox2 is a direct activator of both Socs3 and Fos, as well as possibly Jun and Egr2; furthermore, we provide direct evidence for FOS and JUN binding on Socs3 promoter, suggesting direct transcriptional regulation. These results provide the basis for developing a model of a network of interactions, regulating critical effectors of NSC proliferation and long-term maintenance.

Place, publisher, year, edition, pages
WILEY, 2021
Keywords
AP1 inhibitor T‐ 5224; CRISPR; CUT& RUN; Fos; lentiviral vector; neural stem cells (NSCs); self‐ renewal; Socs3; Sox2; transcription factors
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-174952 (URN)10.1002/stem.3373 (DOI)000634433500001 ()33739574 (PubMedID)
Note

Funding Agencies|Associazione Italiana per la Ricerca sul CancroAssociazione Italiana per la Ricerca sul Cancro (AIRC) [IG 2014 -16016]; European Community ERANET-NEURON [NEURON8-full815-091]

Available from: 2021-04-13 Created: 2021-04-13 Last updated: 2022-03-21Bibliographically approved
Doumpas, N., Söderholm, S., Narula, S., Moreira, S., Doble, B. W., Cantù, C. & Basler, K. (2021). TCF/LEF regulation of the topologically associated domain ADI promotes mESCs to exit the pluripotent ground state. Cell Reports, 36(11), Article ID 109705.
Open this publication in new window or tab >>TCF/LEF regulation of the topologically associated domain ADI promotes mESCs to exit the pluripotent ground state
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2021 (English)In: Cell Reports, E-ISSN 2211-1247, Vol. 36, no 11, article id 109705Article in journal (Refereed) Published
Abstract [en]

Mouse embryonic stem cells (mESCs) can bemaintained in vitro in defined N2B27 medium supplemented with two chemical inhibitors for GSK3 and MEK (2i) and the cytokine leukemia inhibitory factor (LIF), which act synergistically to promote self-renewal and pluripotency. Here, we find that genetic deletion of the four genes encoding the TCF/LEF transcription factors confersm ESCs with the ability to self-renew in N2B27 medium alone. TCF/LEF quadruple knockout (qKO) mESCs display dysregulation of several genes, including Aire, Dnmt3l, and IcosL, located adjacent to each other within a topologically associated domain (TAD). Aire, Dnmt3l, and IcosL appear to be regulated by TCF/LEF in a beta-catenin independent manner. Moreover, downregulation of Aire and Dnmt3l in wild-type mESCs mimics the loss of TCF/LEF and increases mESC survival in the absence of 2iL. Hence, this study identifies TCF/LEF effectors that mediate exit from the pluripotent state.

Place, publisher, year, edition, pages
Cell Press, 2021
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-179646 (URN)10.1016/j.celrep.2021.109705 (DOI)000695832100020 ()34525377 (PubMedID)
Note

Funding Agencies|Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission; Canton of Zurich; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; CancerfondenSwedish Cancer Society [CAN 2018/542]; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR) [MOP133610]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2018-05973]

Available from: 2021-09-30 Created: 2021-09-30 Last updated: 2024-01-17
Fugazza, C., Barbarani, G., Elangovan, S., Marini, M. G., Giolitto, S., Font-Monclus, I., . . . Ronchi, A. E. (2021). The Coup-TFII orphan nuclear receptor is an activator of the γ-globin gene. Haematologica, 106(2), 474-482
Open this publication in new window or tab >>The Coup-TFII orphan nuclear receptor is an activator of the γ-globin gene
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2021 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 106, no 2, p. 474-482Article in journal (Refereed) Published
Abstract [en]

The human fetal γ-globin gene is repressed in the adult stage through complex regulatory mechanisms involving transcription factors and epigenetic modifiers. Reversing γ-globin repression, or maintaining its expression by manipulating regulatory mechanisms, has become a major clinical goal in the treatment of β-hemoglobinopathies. Here, we identify the orphan nuclear receptor Coup-TFII (NR2F2/ARP-1) as an embryonic/fetal stage activator of γ-globin expression. We show that Coup-TFII is expressed in early erythropoiesis of yolk sac origin, together with embryonic/fetal globins. When overexpressed in adult cells (including peripheral blood cells from human healthy donors and β039 thalassemic patients) Coup-TFII activates the embryonic/fetal globins genes, overcoming the repression imposed by the adult erythroid environment. Conversely, the knock-out of Coup-TFII increases the β/γ+β globin ratio. Molecular analysis indicates that Coup-TFII binds in vivo to the β-locus and contributes to its conformation. Overall, our data identify Coup-TFII as a specific activator of the γ-globin gene.

Place, publisher, year, edition, pages
Ferrata Storti Foundation, 2021
Keywords
Hemoglobinopathies, Red Cells, Thalassemia
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-164345 (URN)10.3324/haematol.2019.241224 (DOI)000615780600020 ()32107331 (PubMedID)
Note

Funding: Fondazione CariploFondazione Cariplo [2012.0517]; People Programme (Marie Curie Actions) of the European Unions Seventh Framework Programme FP7/2007-2013/under REA grant [289611]; Knut and Alice Wallenberg foundationKnut & Alice Wallenberg Foundation

Available from: 2020-03-18 Created: 2020-03-18 Last updated: 2021-03-21
Vafaizadeh, V., Buechel, D., Rubinstein, N., Kalathur, R. K. R., Bazzani, L., Saxena, M., . . . Christofori, G. (2021). The interactions of Bcl9/Bcl9L with beta-catenin and Pygopus promote breast cancer growth, invasion, and metastasis. Oncogene, 40(43), 6195-6209
Open this publication in new window or tab >>The interactions of Bcl9/Bcl9L with beta-catenin and Pygopus promote breast cancer growth, invasion, and metastasis
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2021 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 40, no 43, p. 6195-6209Article in journal (Refereed) Published
Abstract [en]

Canonical Wnt/beta-catenin signaling is an established regulator of cellular state and its critical contributions to tumor initiation, malignant tumor progression and metastasis formation have been demonstrated in various cancer types. Here, we investigated how the binding of beta-catenin to the transcriptional coactivators B-cell CLL/lymphoma 9 (Bcl9) and Bcl9-Like (Bcl9L) affected mammary gland carcinogenesis in the MMTV-PyMT transgenic mouse model of metastatic breast cancer. Conditional knockout of both Bcl9 and Bcl9L resulted into tumor cell death. In contrast, disrupting the interaction of Bcl9/Bcl9L with beta-catenin, either by deletion of their HD2 domains or by a point mutation in the N-terminal domain of beta-catenin (D164A), diminished primary tumor growth and tumor cell proliferation and reduced tumor cell invasion and lung metastasis. In comparison, the disruption of HD1 domain-mediated binding of Bcl9/Bcl9L to Pygopus had only moderate effects. Interestingly, interfering with the beta-catenin-Bcl9/Bcl9L-Pygo chain of adapters only partially impaired the transcriptional response of mammary tumor cells to Wnt3a and TGF beta treatments. Together, the results indicate that Bcl9/Bcl9L modulate but are not critically required for canonical Wnt signaling in its contribution to breast cancer growth and malignant progression, a notion consistent with the "just-right" hypothesis of Wnt-driven tumor progression.

Place, publisher, year, edition, pages
Springer Nature, 2021
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-179865 (URN)10.1038/s41388-021-02016-9 (DOI)000698130400001 ()34545187 (PubMedID)
Note

Funding Agencies|SystemsX.ch MTD project MetastasiX [2014/268]; Swiss National Science FoundationSwiss National Science Foundation (SNSF)European Commission [310030B_163471]; Swiss National Science Foundation SinergiaSwiss National Science Foundation (SNSF) [CRSII3_136274]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; CancerfondenSwedish Cancer Society [CAN 2018/542]; Universitat Basel (Universitatsbibliothek Basel)

Available from: 2021-10-06 Created: 2021-10-06 Last updated: 2022-05-24
Varum, S., Baggiolini, A., Zurkirchen, L., Atak, Z. K., Cantù, C., Marzorati, E., . . . Sommer, L. (2019). Yin Yang 1 Orchestrates a Metabolic Program Required for Both Neural Crest Development and Melanoma Formation. Cell Stem Cell, 24(4), 637-653.e9
Open this publication in new window or tab >>Yin Yang 1 Orchestrates a Metabolic Program Required for Both Neural Crest Development and Melanoma Formation
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2019 (English)In: Cell Stem Cell, ISSN 1934-5909, E-ISSN 1875-9777, Vol. 24, no 4, p. 637-653.e9Article in journal (Refereed) Published
Abstract [en]

Increasing evidence suggests that cancer cells highjack developmental programs for disease initiation and progression. Melanoma arises from melanocytes that originate during development from neural crest stem cells (NCSCs). Here, we identified the transcription factor Yin Yang 1 (Yy1) as an NCSCs regulator. Conditional deletion of Yy1 in NCSCs resulted in stage-dependent hypoplasia of all major neural crest derivatives due to decreased proliferation and increased cell death. Moreover, conditional ablation of one Yy1 allele in a melanoma mouse model prevented tumorigenesis, indicating a particular susceptibility of melanoma cells to reduced Yy1 levels. Combined RNA sequencing (RNA-seq), chromatin immunoprecipitation (ChIP)-seq, and untargeted metabolomics demonstrated that YY1 governs multiple metabolic pathways and protein synthesis in both NCSCs and melanoma. In addition to directly regulating a metabolic gene set, YY1 can act upstream of MITF/c-MYC as part of a gene regulatory network controlling metabolism. Thus, both NCSC development and melanoma formation depend on an intricate YY1-controlled metabolic program.

Place, publisher, year, edition, pages
Cell Press, 2019
Keywords
YY1, development, melanoma, metabolism, neural crest, protein synthesis, tumor initiation
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-164344 (URN)10.1016/j.stem.2019.03.011 (DOI)000463353000017 ()30951662 (PubMedID)2-s2.0-85063349622 (Scopus ID)
Available from: 2020-03-18 Created: 2020-03-18 Last updated: 2020-03-24Bibliographically approved
Projects
Organizing REKO: The Viability of a Local Food System in Finland, Sweden & Latvia [22-PR2-0003_OS]; Södertörn University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-1547-5415

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