Of mitogens and morphogens: modelling Sonic Hedgehog mechanisms in vertebrate development

Groves, Ian; Placzek, Marysia; Fletcher, Alexander G.

doi:10.1098/rstb.2019.0660

Cited by 20 publications

(15 citation statements)

References 89 publications

(132 reference statements)

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“…It is a highly conserved evolutionary pathway, almost silent in the adult except for a few tissues such as the skin [4,5]. Specifically, the Hh pathway is a notable example of extracellular morphogenic signal, mitogen, cell survival factor, and axon guidance factor [6][7][8][9]. Recently, the Hh signaling pathway has been recognized as one of the most intensely investigated targets for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance

Nguyen

Cho

2022

IJMS

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Hedgehog (Hh) signaling is a highly conserved pathway that plays a vital role during embryonic development. Recently, uncontrolled activation of this pathway has been demonstrated in various types of cancer. Therefore, Hh pathway inhibitors have emerged as an important class of anti-cancer agents. Unfortunately, however, their reputation has been tarnished by the emergence of resistance during therapy, necessitating clarification of mechanisms underlying the drug resistance. In this review, we briefly overview canonical and non-canonical Hh pathways and their inhibitors as targeted cancer therapy. In addition, we summarize the mechanisms of resistance to Smoothened (SMO) inhibitors, including point mutations of the drug binding pocket or downstream molecules of SMO, and non-canonical mechanisms to reinforce Hh pathway output. A distinct mechanism involving loss of primary cilia is also described to maintain GLI activity in resistant tumors. Finally, we address the main strategies to circumvent the drug resistance. These strategies include the development of novel and potent inhibitors targeting different components of the canonical Hh pathway or signaling molecules of the non-canonical pathway. Further studies are necessary to avoid emerging resistance to Hh inhibitors and establish an optimal customized regimen with improved therapeutic efficacy to treat various types of cancer, including basal cell carcinoma.

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Section: Introductionmentioning

confidence: 99%

Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance

Nguyen

Cho

2022

IJMS

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“…Hedgehog (Hh) proteins are a small family of morphogens that are important for many aspects of embryonic development and are implicated in several diseases [112,113]. As with Wnts, they are lipoglycoproteins.…”

Section: Heparan Sulfate and Wnt Signallingmentioning

confidence: 99%

Syndecan receptors: pericellular regulators in development and inflammatory disease

et al. 2021

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The syndecans are the major family of transmembrane proteoglycans, usually bearing multiple heparan sulfate chains. They are present on virtually all nucleated cells of vertebrates and are also present in invertebrates, indicative of a long evolutionary history. Genetic models in both vertebrates and invertebrates have shown that syndecans link to the actin cytoskeleton and can fine-tune cell adhesion, migration, junction formation, polarity and differentiation. Although often associated as co-receptors with other classes of receptors (e.g. integrins, growth factor and morphogen receptors), syndecans can nonetheless signal to the cytoplasm in discrete ways. Syndecan expression levels are upregulated in development, tissue repair and an array of human diseases, which has led to the increased appreciation that they may be important in pathogenesis not only as diagnostic or prognostic agents, but also as potential targets. Here, their functions in development and inflammatory diseases are summarized, including their potential roles as conduits for viral pathogen entry into cells.

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“…e.g. the homeostatic process and tumorigenesis (101). Gli-1 is considered as a marker when the hedgehog signaling pathway activates abnormally (102).…”

Section: Gastric Cancermentioning

confidence: 99%

Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors

et al. 2021

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Epithelial-to-mesenchymal transition (EMT), a complicated program through which polarized epithelial cells acquire motile mesothelial traits, is regulated by tumor microenvironment. EMT is involved in tumor progression, invasion and metastasis via reconstructing the cytoskeleton and degrading the tumor basement membrane. Accumulating evidence shows that resveratrol, as a non-flavonoid polyphenol, can reverse EMT and inhibit invasion and migration of human tumors via diverse mechanisms and signaling pathways. In the present review, we will summarize the detailed mechanisms and pathways by which resveratrol and its analogs (e.g. Triacetyl resveratrol, 3,5,4’-Trimethoxystilbene) might regulate the EMT process in cancer cells to better understand their potential as novel anti-tumor agents. Resveratrol can also reverse chemoresistance via EMT inhibition and improvement of the antiproliferative effects of conventional treatments. Therefore, resveratrol and its analogs have the potential to become novel adjunctive agents to inhibit cancer metastasis, which might be partly related to their blocking of the EMT process.

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Of mitogens and morphogens: modelling Sonic Hedgehog mechanisms in vertebrate development

Cited by 20 publications

References 89 publications

Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance

Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance

Syndecan receptors: pericellular regulators in development and inflammatory disease

Resveratrol and Its Analogs: Potent Agents to Reverse Epithelial-to-Mesenchymal Transition in Tumors

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