scholarly journals The MAP4K4-STRIPAK complex promotes growth and tissue invasion in medulloblastoma

2021 ◽  
Author(s):  
Jessica Migliavacca ◽  
Buket Zuellig ◽  
Charles Capdeville ◽  
Michael Andreas Grotzer ◽  
Martin Baumgartner

Proliferation and motility are mutually exclusive biological processes associated with cancer that depend on precise control of upstream signaling pathways with overlapping functionalities. We find that STRN3 and STRN4 scaffold subunits of the STRIPAK complex interact with MAP4K4 for pathway regulation in medulloblastoma. Disruption of the MAP4K4-STRIPAK complex impairs growth factor-induced migration and tissue invasion and stalls YAP/TAZ target gene expression and oncogenic growth. The migration promoting functions of the MAP4K4-STRIPAK complex involve the activation of novel PKCs and the phosphorylation of the membrane targeting S157 residue of VASP through MAP4K4. The anti-proliferative effect of complex disruption is associated with reduced YAP/TAZ target gene expression and results in repressed tumor growth in the brain tissue. This dichotomous functionality of the STRIPAK complex in migration and proliferation control acts through MAP4K4 regulation in tumor cells and provides relevant mechanistic insights into novel tumorigenic functions of the STRIPAK complex in medulloblastoma.

2006 ◽  
Vol 26 (16) ◽  
pp. 6283-6298 ◽  
Author(s):  
Maria Kasper ◽  
Harald Schnidar ◽  
Graham W. Neill ◽  
Michaela Hanneder ◽  
Stefan Klingler ◽  
...  

ABSTRACT Hedgehog (HH)/GLI signaling plays a critical role in epidermal development and basal cell carcinoma. Here, we provide evidence that epidermal growth factor receptor (EGFR) signaling modulates the target gene expression profile of GLI transcription factors in epidermal cells. Using expression profiling and quantitative reverse transcriptase PCR, we identified a set of 19 genes whose transcription is synergistically induced by GLI1 and parallel EGF treatment. Promoter studies of a subset of GLI/EGF-regulated genes, including the genes encoding interleukin-1 antagonist IL1R2, Jagged 2, cyclin D1, S100A7, and S100A9, suggest convergence of EGFR and HH/GLI signaling at the level of promoters of selected direct GLI target genes. Inhibition of EGFR and MEK/ERK but not of phosphatidylinositol 3-kinase/AKT abrogated synergistic activation of GLI/EGF target genes, showing that EGFR can signal via RAF/MEK/ERK to cooperate with GLI proteins in selective target gene regulation. Coexpression of the GLI/EGF target IL1R2, EGFR, and activated ERK1/2 in human anagen hair follicles argues for a cooperative role of EGFR and HH/GLI signaling in specifying the fate of outer root sheath (ORS) cells. We also show that EGF treatment neutralizes GLI-mediated induction of epidermal stem cell marker expression and provide evidence that EGFR signaling is essential for GLI-induced cell cycle progression in epidermal cells. The results suggest that EGFR signaling modulates GLI target gene profiles which may play an important regulatory role in ORS specification, hair growth, and possibly cancer.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2049-P
Author(s):  
REBECCA K. DAVIDSON ◽  
NOLAN CASEY ◽  
JASON SPAETH

Author(s):  
Philipp Moritz Fricke ◽  
Angelika Klemm ◽  
Michael Bott ◽  
Tino Polen

Abstract Acetic acid bacteria (AAB) are valuable biocatalysts for which there is growing interest in understanding their basics including physiology and biochemistry. This is accompanied by growing demands for metabolic engineering of AAB to take advantage of their properties and to improve their biomanufacturing efficiencies. Controlled expression of target genes is key to fundamental and applied microbiological research. In order to get an overview of expression systems and their applications in AAB, we carried out a comprehensive literature search using the Web of Science Core Collection database. The Acetobacteraceae family currently comprises 49 genera. We found overall 6097 publications related to one or more AAB genera since 1973, when the first successful recombinant DNA experiments in Escherichia coli have been published. The use of plasmids in AAB began in 1985 and till today was reported for only nine out of the 49 AAB genera currently described. We found at least five major expression plasmid lineages and a multitude of further expression plasmids, almost all enabling only constitutive target gene expression. Only recently, two regulatable expression systems became available for AAB, an N-acyl homoserine lactone (AHL)-inducible system for Komagataeibacter rhaeticus and an l-arabinose-inducible system for Gluconobacter oxydans. Thus, after 35 years of constitutive target gene expression in AAB, we now have the first regulatable expression systems for AAB in hand and further regulatable expression systems for AAB can be expected. Key points • Literature search revealed developments and usage of expression systems in AAB. • Only recently 2 regulatable plasmid systems became available for only 2 AAB genera. • Further regulatable expression systems for AAB are in sight.


2002 ◽  
Vol 88 (2) ◽  
pp. 363-371 ◽  
Author(s):  
Aruna V. Krishnan ◽  
Donna M. Peehl ◽  
David Feldman

2014 ◽  
Vol 10 (1) ◽  
pp. 109-114 ◽  
Author(s):  
Garrett S. Gibbons ◽  
Scott R. Owens ◽  
Eric R. Fearon ◽  
Zaneta Nikolovska-Coleska

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