Non-cell-autonomous signaling by Shh in tumors: challenges and opportunities for therapeutic targets
Open accessAbstract
IMPORTANCE OF THE FIELD: The Hedgehog (Hh) pathway is required during many developmental events; in adults the Hedgehog pathway is involved in the maintenance of several stem cell niches. It is therefore not surprising that aberrantly regulated Hh pathway activity can cause birth defects in the developing organism, as well as neoplastic disease later in life. AREAS COVERED IN THIS REVIEW: As a consequence of the involvement in pathogenesis, the Hh pathway components are subject to an intense scrutiny as potential targets for therapeutic agents. We aim to provide an overview of the biology of the Hh proteins and the cellular response, in conjunction with potential therapeutic interventions. WHAT THE READER WILL GAIN: Specifically, we focus on the recently discovered non-cell-autonomous Shh signaling used by tumors and the implications of this for the design of treatment strategies. This should provide the reader with up-to-date knowledge on the role of the Hh pathway in tumor progression and the options to treat these malignancies. TAKE HOME MESSAGE: An important concept that we advocate in this review is the need to recognize the need to target both the stromal and the tumor compartment in malignancies that rely on paracrine Shh signaling.
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IFT80 can repress SHH-mediated noncanonical activation of the GTPase RHOA in differentiating mouse osteoblasts.
“For example, the IFT-B complex protein, IFT80, can repress SHH-mediated noncanonical activation of the GTPase RHOA in differentiating mouse osteoblasts 108,”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [108]
The Hedgehog signal transduction section describes a transcription-independent Shh response, supporting the general reference to noncanonical signaling. It does not identify IFT80, RHOA, or differentiating mouse osteoblasts, so it does not support the specific repression mechanism claimed. Page numbers are unavailable in our copy. (LLM, conf=0.81)
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Cellular signalling by primary cilia in development, organ function and disease
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- Authors
- Bijlsma, M. F., & Roelink, H.
- Affiliations
- University of California, Berkeley (US)
- Corresponding author
- Roelink, Henk
- Venue
- Expert Opinion on Therapeutic Targets
- Publisher
- Informa Healthcare
- Published
- 2010-06
- Volume
- 14
- Issue
- 7
- Pages
- 693-702
- ISSN
- 1472-8222 (ISSN-L)
- 1744-7631
- PMC
- PMC8480204
- OpenAlex
- W1988419972
- Cited by
- 11
- References
- 89
- Citations by year
- 2024: 1 · 2019: 1 · 2016: 2 · 2015: 4 · 2014: 3
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Expert Opinion on Therapeutic Targets (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM097035)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Sonic hedgehog, Hedgehog signaling, non-cell-autonomous signaling, paracrine signaling, tumor microenvironment, tumor stroma, therapeutic target, tumor progression, cancer therapy
- MeSH terms
- Acylation, Animals, Antineoplastic Agents, Endocytosis, Humans, Ligands, Neoplasms, Protein Processing, Post-Translational, Stromal Cells, Paracrine Communication, Intercellular Signaling Peptides and Proteins, Hedgehog Proteins, Stem Cell Niche, Secretory Pathway
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