title: hMOB3 modulates MST1 apoptotic signaling and supports tumor growth in glioblastoma multiforme.
abstract: New therapeutic targets are needed that circumvent inherent therapeutic resistance of glioblastoma multiforme (GBM). Here, we report such a candidate target in the uncharacterized adaptor protein hMOB3, which we show is upregulated in GBM. In a search for its biochemical function, we found that hMOB3 specifically interacts with MST1 kinase in response to apoptotic stimuli and cell-cell contact. Moreover, hMOB3 negatively regulated apoptotic signaling by MST1 in GBM cells by inhibiting the MST1 cleavage-based activation process. Physical interaction between hMOB3 and MST1 was essential for this process. In vivo investigations established that hMOB3 sustains GBM cell growth at high cell density and promotes tumorigenesis. Our results suggest hMOB3 as a candidate therapeutic target for the treatment of malignant gliomas.
authors.affiliation: Authors' Affiliations: Friedrich Miescher Institute for Biomedical Research; debora.schmitz@fmi.ch fengyuan.tang@fmi.ch.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Tang
authors.affiliation: Authors' Affiliations: Friedrich Miescher Institute for Biomedical Research;
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Authors' Affiliations: Friedrich Miescher Institute for Biomedical Research;
authors.forename: Gongda
authors.initials: G
authors.lastname: Xue
authors.affiliation: Authors' Affiliations: Friedrich Miescher Institute for Biomedical Research;
authors.forename: Debby
authors.initials: D
authors.lastname: Hynx
authors.affiliation: Authors' Affiliations: Friedrich Miescher Institute for Biomedical Research;
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Authors' Affiliations: Friedrich Miescher Institute for Biomedical Research;
authors.forename: Peter D
authors.initials: PD
authors.lastname: Cron
authors.affiliation: Authors' Affiliations: Friedrich Miescher Institute for Biomedical Research; Swiss Institute of Bioinformatics, Basel, Switzerland; and.
authors.forename: Christian
authors.initials: C
authors.lastname: Hundsrucker
authors.affiliation: Cancer Institute University College London, London, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hergovich
authors.affiliation: Division of Neuropathology, Institute of Pathology, University of Basel;
authors.forename: Stephan
authors.initials: S
authors.lastname: Frank
authors.affiliation: Authors' Affiliations: Friedrich Miescher Institute for Biomedical Research;
authors.forename: Brian A
authors.initials: BA
authors.lastname: Hemmings
authors.affiliation: Authors' Affiliations: Friedrich Miescher Institute for Biomedical Research; debora.schmitz@fmi.ch fengyuan.tang@fmi.ch.
authors.forename: Debora
authors.initials: D
authors.lastname: Schmitz-Rohmer
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015870:Gene Expression; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D047368:Tumor Burden
chemical_list: C475491:MAP1B protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor