BAG3 is a negative regulator of ciliogenesis in glioblastoma and triple-negative breast cancer cells

  • By regulating several hallmarks of cancer, BAG3 exerts oncogenic functions in a wide variety of malignant diseases including glioblastoma (GBM) and triple-negative breast cancer (TNBC). Here we performed global proteomic/phosphoproteomic analyses of CRISPR/Cas9-mediated isogenic BAG3 knockouts of the two GBM lines U343 and U251 in comparison to parental controls. Depletion of BAG3 evoked major effects on proteins involved in ciliogenesis/ciliary function and the activity of the related kinases aurora-kinase A and CDK1. Cilia formation was significantly enhanced in BAG3 KO cells, a finding that could be confirmed in BAG3-deficient versus -proficient BT-549 TNBC cells, thus identifying a completely novel function of BAG3 as a negative regulator of ciliogenesis. Furthermore, we demonstrate that enhanced ciliogenesis and reduced expression of SNAI1 and ZEB1, two key transcription factors regulating epithelial to mesenchymal transition (EMT) are correlated to decreased cell migration, both in the GBM and TNBC BAG3 knockout cells. Our data obtained in two different tumor entities identify suppression of EMT and ciliogenesis as putative synergizing mechanisms of BAG3-driven tumor aggressiveness in therapy-resistant cancers.
Author:Benedikt LinderORCiDGND, Caterina Klein, Marina E. Hoffmann, Florian Bonn, Ivan ĐikićORCiDGND, Donat KögelORCiD
Parent Title (English):Journal of cellular biochemistry
Place of publication:New York, NY
Document Type:Article
Date of Publication (online):2021/06/27
Date of first Publication:2021/06/27
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/03/09
Tag:BAG3; cell migration; epithelial to mesenchymal transition; glioblastoma; primary cilium; triple-negative breast cancer
Page Number:14
First Page:77
Last Page:90
This study is supported by a grant from the Deutsche Forschungsgemeinschaft (German Research Foundation, KO 1898/11-1) to Donat Kögel.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0