Next Article in Journal
Uveal Melanoma
Next Article in Special Issue
Bone Morphogenetic Protein 4 Targeting Glioma Stem-Like Cells for Malignant Glioma Treatment: Latest Advances and Implications for Clinical Application
Previous Article in Journal
Stabilization of Hypoxia-Inducible Factors and BNIP3 Promoter Methylation Contribute to Acquired Sorafenib Resistance in Human Hepatocarcinoma Cells
Previous Article in Special Issue
Molecular Imaging in Pediatric Brain Tumors
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Cancers
Volume 11
Issue 12
10.3390/cancers11121985
cancers-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Crosstalk between SHH and FGFR Signaling Pathways Controls Tissue Invasion in Medulloblastoma

by
Anuja Neve
1,†,
Jessica Migliavacca
1,†,
Charles Capdeville
1,†,
Marc Thomas Schönholzer
1,
Alexandre Gries
1,
Min Ma
2,
Karthiga Santhana Kumar
1,
Michael Grotzer
1 and
Martin Baumgartner
1,*
1
Department of Oncology, University Children’s Hospital Zürich, CH-8032 Zürich, Switzerland
2
Faculty of Biology and Medicine, University of Lausanne, Biochemistry, CH-1066 Epalinges, Switzerland
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2019, 11(12), 1985; https://doi.org/10.3390/cancers11121985
Submission received: 31 October 2019 / Revised: 25 November 2019 / Accepted: 6 December 2019 / Published: 10 December 2019
(This article belongs to the Special Issue Pediatric Brain Tumor)
Browse Figures
Review Reports Versions Notes

Abstract

In the Sonic Hedgehog (SHH) subgroup of medulloblastoma (MB), tumor initiation and progression are in part driven by smoothened (SMO) and fibroblast growth factor (FGF)-receptor (FGFR) signaling, respectively. We investigated the impact of the SMO-FGFR crosstalk on tumor growth and invasiveness in MB. We found that FGFR signaling represses GLI1 expression downstream of activated SMO in the SHH MB line DAOY and induces MKI67, HES1, and BMI1 in DAOY and in the group 3 MB line HD-MBO3. FGFR repression of GLI1 does not affect proliferation or viability, whereas inhibition of FGFR is necessary to release SMO-driven invasiveness. Conversely, SMO activation represses FGFR-driven sustained activation of nuclear ERK. Parallel activation of FGFR and SMO in ex vivo tumor cell-cerebellum slice co-cultures reduced invasion of tumor cells without affecting proliferation. In contrast, treatment of the cells with the SMO antagonist Sonidegib (LDE225) blocked invasion and proliferation in cerebellar slices. Thus, sustained, low-level SMO activation is necessary for proliferation and tissue invasion, whereas acute, pronounced activation of SMO can repress FGFR-driven invasiveness. This suggests that the tumor cell response is dependent on the relative local abundance of the two factors and indicates a paradigm of microenvironmental control of invasion in SHH MB through mutual control of SHH and FGFR signaling.
Keywords: medulloblastoma; FGFR; Sonic Hedgehog signaling; organotypic culture; cell invasion; signal crosstalk; MAP kinase signaling medulloblastoma; FGFR; Sonic Hedgehog signaling; organotypic culture; cell invasion; signal crosstalk; MAP kinase signaling
Graphical Abstract

Share and Cite

MDPI and ACS Style

Neve, A.; Migliavacca, J.; Capdeville, C.; Schönholzer, M.T.; Gries, A.; Ma, M.; Santhana Kumar, K.; Grotzer, M.; Baumgartner, M. Crosstalk between SHH and FGFR Signaling Pathways Controls Tissue Invasion in Medulloblastoma. Cancers 2019, 11, 1985. https://doi.org/10.3390/cancers11121985

AMA Style

Neve A, Migliavacca J, Capdeville C, Schönholzer MT, Gries A, Ma M, Santhana Kumar K, Grotzer M, Baumgartner M. Crosstalk between SHH and FGFR Signaling Pathways Controls Tissue Invasion in Medulloblastoma. Cancers. 2019; 11(12):1985. https://doi.org/10.3390/cancers11121985

Chicago/Turabian Style

Neve, Anuja, Jessica Migliavacca, Charles Capdeville, Marc Thomas Schönholzer, Alexandre Gries, Min Ma, Karthiga Santhana Kumar, Michael Grotzer, and Martin Baumgartner. 2019. "Crosstalk between SHH and FGFR Signaling Pathways Controls Tissue Invasion in Medulloblastoma" Cancers 11, no. 12: 1985. https://doi.org/10.3390/cancers11121985

APA Style

Neve, A., Migliavacca, J., Capdeville, C., Schönholzer, M. T., Gries, A., Ma, M., Santhana Kumar, K., Grotzer, M., & Baumgartner, M. (2019). Crosstalk between SHH and FGFR Signaling Pathways Controls Tissue Invasion in Medulloblastoma. Cancers, 11(12), 1985. https://doi.org/10.3390/cancers11121985

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop