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Hedgehog signaling in cancer stem cells: a focus on hematological cancers.

Campbell V, Copland M - Stem Cells Cloning (2015)

Bottom Line: The stem cell paradigm was first demonstrated in hematopoietic stem cells.Further, these components represent viable therapeutic targets, with inhibition from a drug development perspective being readily achieved, making the hedgehog pathway an attractive potential therapeutic target.However, although the concept of cancer stem cells is well established, how these cells arise and the factors which influence their behavior are not yet fully understood.

View Article: PubMed Central - PubMed

Affiliation: Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterninary and Life Sciences, University of Glasgow, Glasgow, UK.

ABSTRACT
The stem cell paradigm was first demonstrated in hematopoietic stem cells. Whilst classically it was cytokines and chemokines which were believed to control stem cell fate, more recently it has become apparent that the stem cell niche and highly conserved embryonic pathways play a key role in governing stem cell behavior. One of these pathways, the hedgehog signaling pathway, found in all organisms, is vitally important in embryogenesis, performing the function of patterning through early stages of development, and in adulthood, through the control of somatic stem cell numbers. In addition to these roles in health however, it has been found to be deregulated in a number of solid and hematological malignancies, components of the hedgehog pathway being associated with a poor prognosis. Further, these components represent viable therapeutic targets, with inhibition from a drug development perspective being readily achieved, making the hedgehog pathway an attractive potential therapeutic target. However, although the concept of cancer stem cells is well established, how these cells arise and the factors which influence their behavior are not yet fully understood. The role of the hedgehog signaling pathway and its potential as a therapeutic target in hematological malignancies is the focus of this review.

No MeSH data available.


Related in: MedlinePlus

Non-canonical Hh signaling.Note: The Hh pathway can be activated directly through PTCH1 or SMO, or via alternative pathways including the PI3K/AKT and RAS/RAF/MEK/ERK signaling cascades.Abbreviations: Hh, hedgehog; EMT, epithelial-mesenchymal transition; PTCH1, Patched 1; SMO, Smoothened.
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f2-sccaa-8-027: Non-canonical Hh signaling.Note: The Hh pathway can be activated directly through PTCH1 or SMO, or via alternative pathways including the PI3K/AKT and RAS/RAF/MEK/ERK signaling cascades.Abbreviations: Hh, hedgehog; EMT, epithelial-mesenchymal transition; PTCH1, Patched 1; SMO, Smoothened.

Mentions: The notion of non-canonical signaling has arisen following observations that the pathway response does not always appear to follow the classical canonical signaling paradigm, although the evidence is not conclusive. Three scenarios of non-canonical Hh signaling have been described, Figure 2: direct interaction with components of other pathways, atypical interaction of components, and activity independent of GLI-mediated transcription, defined as Type I (PTCH-dependent) and Type II (SMO-dependent).36 In reality, it is likely the canonical and non-canonical pathways act in parallel.


Hedgehog signaling in cancer stem cells: a focus on hematological cancers.

Campbell V, Copland M - Stem Cells Cloning (2015)

Non-canonical Hh signaling.Note: The Hh pathway can be activated directly through PTCH1 or SMO, or via alternative pathways including the PI3K/AKT and RAS/RAF/MEK/ERK signaling cascades.Abbreviations: Hh, hedgehog; EMT, epithelial-mesenchymal transition; PTCH1, Patched 1; SMO, Smoothened.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325629&req=5

f2-sccaa-8-027: Non-canonical Hh signaling.Note: The Hh pathway can be activated directly through PTCH1 or SMO, or via alternative pathways including the PI3K/AKT and RAS/RAF/MEK/ERK signaling cascades.Abbreviations: Hh, hedgehog; EMT, epithelial-mesenchymal transition; PTCH1, Patched 1; SMO, Smoothened.
Mentions: The notion of non-canonical signaling has arisen following observations that the pathway response does not always appear to follow the classical canonical signaling paradigm, although the evidence is not conclusive. Three scenarios of non-canonical Hh signaling have been described, Figure 2: direct interaction with components of other pathways, atypical interaction of components, and activity independent of GLI-mediated transcription, defined as Type I (PTCH-dependent) and Type II (SMO-dependent).36 In reality, it is likely the canonical and non-canonical pathways act in parallel.

Bottom Line: The stem cell paradigm was first demonstrated in hematopoietic stem cells.Further, these components represent viable therapeutic targets, with inhibition from a drug development perspective being readily achieved, making the hedgehog pathway an attractive potential therapeutic target.However, although the concept of cancer stem cells is well established, how these cells arise and the factors which influence their behavior are not yet fully understood.

View Article: PubMed Central - PubMed

Affiliation: Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medical, Veterninary and Life Sciences, University of Glasgow, Glasgow, UK.

ABSTRACT
The stem cell paradigm was first demonstrated in hematopoietic stem cells. Whilst classically it was cytokines and chemokines which were believed to control stem cell fate, more recently it has become apparent that the stem cell niche and highly conserved embryonic pathways play a key role in governing stem cell behavior. One of these pathways, the hedgehog signaling pathway, found in all organisms, is vitally important in embryogenesis, performing the function of patterning through early stages of development, and in adulthood, through the control of somatic stem cell numbers. In addition to these roles in health however, it has been found to be deregulated in a number of solid and hematological malignancies, components of the hedgehog pathway being associated with a poor prognosis. Further, these components represent viable therapeutic targets, with inhibition from a drug development perspective being readily achieved, making the hedgehog pathway an attractive potential therapeutic target. However, although the concept of cancer stem cells is well established, how these cells arise and the factors which influence their behavior are not yet fully understood. The role of the hedgehog signaling pathway and its potential as a therapeutic target in hematological malignancies is the focus of this review.

No MeSH data available.


Related in: MedlinePlus