Hahn, Heidi Eva

[["dc.bibliographiccitation.journal","Frontiers in Pediatrics"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Ragab, Nada"],["dc.contributor.author","Viehweger, Florian"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Geyer, Natalie"],["dc.contributor.author","Yang, Mingya"],["dc.contributor.author","Seils, Anna"],["dc.contributor.author","Belharazem, Djeda"],["dc.contributor.author","Brembeck, Felix H."],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Simon-Keller, Katja"],["dc.date.accessioned","2020-12-10T18:44:36Z"],["dc.date.available","2020-12-10T18:44:36Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.3389/fped.2018.00378"],["dc.identifier.eissn","2296-2360"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78522"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Canonical WNT/β-Catenin Signaling Plays a Subordinate Role in Rhabdomyosarcomas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","International Journal of Oncology"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Ragab, Nada"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Marx, Alexander"],["dc.contributor.author","Hahn, Heidi"],["dc.contributor.author","Simon-Keller, Katja"],["dc.date.accessioned","2022-09-01T09:51:17Z"],["dc.date.available","2022-09-01T09:51:17Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.3892/ijo.2022.5392"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113925"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","1791-2423"],["dc.relation.issn","1019-6439"],["dc.title","Tumor suppressive functions of WNT5A in rhabdomyosarcoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1556"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of Investigative Dermatology"],["dc.bibliographiccitation.lastpage","1565.e11"],["dc.bibliographiccitation.volume","140"],["dc.contributor.author","Becker, Marco"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Pyczek, Joanna"],["dc.contributor.author","König, Simone"],["dc.contributor.author","Müllen, Anna"],["dc.contributor.author","Rabe, Hanna"],["dc.contributor.author","Schön, Michael P."],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2021-04-14T08:24:35Z"],["dc.date.available","2021-04-14T08:24:35Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.jid.2019.11.030"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81343"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.issn","0022-202X"],["dc.title","WIF1 Suppresses the Generation of Suprabasal Cells in Acanthotic Skin and Growth of Basal Cell Carcinomas upon Forced Overexpression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Oncogene"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Cuvelier, Nicole"],["dc.contributor.author","Ragab, Nada"],["dc.contributor.author","Simon-Keller, Katja"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Geyer, Natalie"],["dc.contributor.author","Botermann, Dominik S."],["dc.contributor.author","Elmer, Dominik P."],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2021-07-05T15:00:28Z"],["dc.date.available","2021-07-05T15:00:28Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract A prototypic pediatric cancer that frequently shows activation of RAS signaling is embryonal rhabdomyosarcoma (ERMS). ERMS also show aberrant Hedgehog (HH)/GLI signaling activity and can be driven by germline mutations in this pathway. We show, that in ERMS cell lines derived from sporadic tumors i.e. from tumors not caused by an inherited genetic variant, HH/GLI signaling plays a subordinate role, because oncogenic mutations in HRAS , KRAS , or NRAS (collectively named oncRAS) inhibit the main HH target GLI1 via the MEK/ERK-axis, but simultaneously increase proliferation and tumorigenicity. oncRAS also modulate expression of stem cell markers in an isoform- and context-dependent manner. In Hh -driven murine ERMS that are caused by a Patched mutation, oncHRAS and mainly oncKRAS accelerate tumor development, whereas oncNRAS induces a more differentiated phenotype. These features occur when the oncRAS mutations are induced at the ERMS precursor stage, but not when induced in already established tumors. Moreover, in contrast to what is seen in human cell lines, oncRAS mutations do not alter Hh signaling activity and marginally affect expression of stem cell markers. Together, all three oncRAS mutations seem to be advantageous for ERMS cell lines despite inhibition of HH signaling and isoform-specific modulation of stem cell markers. In contrast, oncRAS mutations do not inhibit Hh-signaling in Hh-driven ERMS. In this model, oncRAS mutations seem to be advantageous for specific ERMS populations that occur within a specific time window during ERMS development. In addition, this window may be different for individual oncRAS isoforms, at least in the mouse."],["dc.description.abstract","Abstract A prototypic pediatric cancer that frequently shows activation of RAS signaling is embryonal rhabdomyosarcoma (ERMS). ERMS also show aberrant Hedgehog (HH)/GLI signaling activity and can be driven by germline mutations in this pathway. We show, that in ERMS cell lines derived from sporadic tumors i.e. from tumors not caused by an inherited genetic variant, HH/GLI signaling plays a subordinate role, because oncogenic mutations in HRAS , KRAS , or NRAS (collectively named oncRAS) inhibit the main HH target GLI1 via the MEK/ERK-axis, but simultaneously increase proliferation and tumorigenicity. oncRAS also modulate expression of stem cell markers in an isoform- and context-dependent manner. In Hh -driven murine ERMS that are caused by a Patched mutation, oncHRAS and mainly oncKRAS accelerate tumor development, whereas oncNRAS induces a more differentiated phenotype. These features occur when the oncRAS mutations are induced at the ERMS precursor stage, but not when induced in already established tumors. Moreover, in contrast to what is seen in human cell lines, oncRAS mutations do not alter Hh signaling activity and marginally affect expression of stem cell markers. Together, all three oncRAS mutations seem to be advantageous for ERMS cell lines despite inhibition of HH signaling and isoform-specific modulation of stem cell markers. In contrast, oncRAS mutations do not inhibit Hh-signaling in Hh-driven ERMS. In this model, oncRAS mutations seem to be advantageous for specific ERMS populations that occur within a specific time window during ERMS development. In addition, this window may be different for individual oncRAS isoforms, at least in the mouse."],["dc.identifier.doi","10.1038/s41388-021-01904-4"],["dc.identifier.pii","1904"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87833"],["dc.language.iso","en"],["dc.notes.intern","DOI Import DOI-Import GROB-441"],["dc.relation.eissn","1476-5594"],["dc.relation.issn","0950-9232"],["dc.title","Context-dependent modulation of aggressiveness of pediatric tumors by individual oncogenic RAS isoforms"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Genetics"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Pyczek, Joanna"],["dc.contributor.author","Khizanishvili, Natalia"],["dc.contributor.author","Kuzyakova, Maria"],["dc.contributor.author","Zabel, Sebastian"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Nitzki, Frauke"],["dc.contributor.author","Emmert, Steffen"],["dc.contributor.author","Schön, Michael P."],["dc.contributor.author","Boukamp, Petra"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2020-12-10T18:44:24Z"],["dc.date.available","2020-12-10T18:44:24Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.3389/fgene.2019.01185"],["dc.identifier.eissn","1664-8021"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16829"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78434"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Regulation and Role of GLI1 in Cutaneous Squamous Cell Carcinoma Pathogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","396"],["dc.bibliographiccitation.journal","Frontiers in Oncology"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Geyer, Natalie"],["dc.contributor.author","Ridzewski, Rosalie"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Kuzyakova, Maria"],["dc.contributor.author","Dittmann, Kai"],["dc.contributor.author","Dullin, Christian"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Fulda, Simone"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2019-07-09T11:50:33Z"],["dc.date.available","2019-07-09T11:50:33Z"],["dc.date.issued","2018"],["dc.description.abstract","Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma with poor prognosis. RMS frequently show Hedgehog (HH) pathway activity, which is predominantly seen in the embryonal subtype (ERMS). They also show activation of Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling. Here we compared the therapeutic effectiveness and the impact on HH target gene expression of Smoothened (SMO) antagonists with those of the PI3K inhibitor pictilisib in ERMS with and without mutations in the HH receptor Patched1 (PTCH). Our data demonstrate that growth of ERMS showing canonical Hh signaling activity due to Ptch germline mutations is efficiently reduced by SMO antagonists. This goes along with strong downregulation of the Hh target Gli1. Likewise Ptch mutant tumors are highly responsive toward the PI3K inhibitor pictilisib, which involves modulation of AKT and caspase activity. Pictilisib also modulates Hh target gene expression, which, however, is rather not correlated with its antitumoral effects. In contrast, sporadic ERMS, which usually express HH target genes without having PTCH mutation, apparently lack canonical HH signaling activity. Thus, stimulation by Sonic HE (SHH) or SAG (Smoothened agonist) or inhibition by SMO antagonists do not modulate HH target gene expression. In addition, SMO antagonists do not provoke efficient anticancer effects and rather exert off-target effects. In contrast, pictilisib and other PI3K/AKT/mTOR inhibitors potently inhibit cellular growth. They also efficiently inhibit HH target gene expression. However, of whether this is correlated with their antitumoral effects it is not clear. Together, these data suggest that PI3K inhibitors are a good and reliable therapeutic option for all ERMS, whereas SMO inhibitors might only be beneficial for ERMS driven by PTCH mutations."],["dc.identifier.doi","10.3389/fonc.2018.00396"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15965"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59798"],["dc.language.iso","en"],["dc.subject.ddc","610"],["dc.title","Different Response of Ptch Mutant and Ptch Wildtype Rhabdomyosarcoma Toward SMO and PI3K Inhibitors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","13377"],["dc.bibliographiccitation.issue","24"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Ragab, Nada"],["dc.contributor.author","Bauer, Julia"],["dc.contributor.author","Botermann, Dominik S."],["dc.contributor.author","Uhmann, Anja"],["dc.contributor.author","Hahn, Heidi"],["dc.date.accessioned","2022-01-11T14:08:09Z"],["dc.date.available","2022-01-11T14:08:09Z"],["dc.date.issued","2021"],["dc.date.updated","2022-09-03T23:24:46Z"],["dc.description.abstract","In the Ptch+/- mouse model for embryonal rhabdomyosarcoma (ERMS), we recently showed that oncogenic (onc) H-, K- or NRAS mutations do not influence tumor growth when induced at the advanced, full-blown tumor stage. However, when induced at the invisible ERMS precursor stage at 4 weeks of age, tumor development was enforced upon oncHRAS and oncKRAS but not by oncNRAS, which instead initiated tumor differentiation. These data indicate that oncRAS-associated processes differ from each other in dependency on the isoform and their occurrence during tumor development. Here, we investigated the outcome of oncNRAS induction at an earlier ERMS precursor stage at 2 weeks of age. In this setting, oncNRAS accelerates tumor growth because it significantly shortens the ERMS-free survival and increases the ERMS incidence. However, it does not seem to alter the differentiation of the tumors. It is also not involved in tumor initiation. Together, these data show that oncNRAS mutations can accelerate tumor growth when targeting immature ERMS precursors within a specific time window, in which the precursors are permissive to the mutation and show that oncNRAS-associated processes differ from each other in dependency on their occurrence during tumor development."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3390/ijms222413377"],["dc.identifier.pii","ijms222413377"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97949"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Oncogenic NRAS Accelerates Rhabdomyosarcoma Formation When Occurring within a Specific Time Frame during Tumor Development in Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]