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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480204 | PMC |
| http://dx.doi.org/10.1517/14728222.2010.497488 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tegaserod maleate exerts anti-tumor effects on prostate cancer via repressing sonic hedgehog signaling pathway.
Mol Med
January 2025
Department of Urology, The Fifth Affiliated Hospital of Southern Medical University, Guangzhou, 510920, Guangdong, People's Republic of China.
Prostate cancer (PCa) is a highly common type of malignancy and affects millions of men in the world since it is easy to recur or emerge therapy resistance. Therefore, it is urgent to find novel treatments for PCa patients. In the current study, we found that tegaserod maleate (TM), an FDA-approved agent, inhibited proliferation, colony formation, migration as well as invasion, caused the arrest of the cell cycle, and promoted apoptosis of PCa cells in vitro.
View Article and Find Full Text PDFPDE4 inhibitor rolipram represses hedgehog signaling via ubiquitin-mediated proteolysis of GLI transcription factors to regress breast cancer.
J Biol Chem
January 2025
Cell and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani, Nadia, West Bengal, India, 741235. Electronic address:
Aberrant activation of the hedgehog (Hh) signaling pathway positively correlates with progression, invasion and metastasis of several cancers, including breast cancer. Although numerous inhibitors of the Hh signaling pathway are available, several oncogenic mutations of key components of the pathway, including Smoothened (Smo), have limited their capability to be developed as putative anti-cancer drugs. In this study, we have modulated the Hh signaling pathway in breast cancer using a specific FDA-approved phosphodiesterase 4 (PDE4) inhibitor rolipram.
View Article and Find Full Text PDFParadoxical effects of inhibition of Δ14-reductase and Δ7-reductase on porcine oocyte maturation and subsequent embryo development after parthenogenetic activation.
Theriogenology
January 2025
Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, 08826, Seoul, Republic of Korea. Electronic address:
Follicular fluid-derived meiosis-activating sterol (FF-MAS), an intermediate in the cholesterol biosynthesis pathway, plays a crucial role in the meiotic resumption of mammalian oocytes. Maintaining a high concentration of FF-MAS in vitro is challenging; therefore, AY9944 A-7, an inhibitor of Δ14-reductase [which converts FF-MAS to testis meiosis-activating sterol (T-MAS)] and Δ7-reductase (which converts T-MAS to cholesterol), has been used to enhance oocyte maturation. This study examined the effects of various concentrations (0, 10, 20, and 40 μM) of AY9944 A-7 on porcine oocyte maturation and subsequent embryo development.
View Article and Find Full Text PDFType 3 deiodinase activation mediated by the Shh/Gli1 axis promotes sepsis-induced metabolic dysregulation in skeletal muscles.
Burns Trauma
January 2025
Department of Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Gulou District, Nanjing, Jiangsu 210008, China.
Background: Non-thyroidal illness syndrome is commonly observed in critically ill patients, characterized by the inactivation of systemic thyroid hormones (TH), which aggravates metabolic dysfunction. Recent evidence indicates that enhanced TH inactivation is mediated by the reactivation of type 3 deiodinase (Dio3) at the tissue level, culminating in a perturbed local metabolic equilibrium. This study assessed whether targeted inhibition of Dio3 can maintain tissue metabolic homeostasis under septic conditions and explored the mechanism behind Dio3 reactivation.
View Article and Find Full Text PDFEndogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.
Proc Natl Acad Sci U S A
February 2025
Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!