Abstract
Cancer stem cells (CSCs) represent a rare population of cells with the capacity to self-renew and give rise to heterogeneous cell lineages within a tumour. Whilst the mechanisms underlying the regulation of CSCs are poorly defined, key developmental signaling pathways required for normal stem and progenitor functions have been strongly implicated. Hedgehog (Hh) signaling is an evolutionarily-conserved pathway essential for self-renewal and cell fate determination. Aberrant Hh signaling is associated with the development and progression of various types of cancer and is implicated in multiple aspects of tumourigenesis, including the maintenance of CSCs. Here, we discuss the mounting evidence suggestive of Hh-driven CSCs in the context of haematological malignancies and solid tumours and the novel strategies that hold the potential to block many aspects of the transformation attributed to the CSC phenotype, including chemotherapeutic resistance, relapse and metastasis.
Highlights
Cancer is a term encompassing a broad spectrum of disease uniformly defined by uncontrolled growth and underpinned by genomic instability, leading to further genetic diversity and intratumoural cellular and functional heterogeneity
This review focuses on the evidence that exists in favour of the cancer stem cells (CSCs) model, the role of the Hedgehog pathway in
The association between Hh signaling and tumourigenesis was initially established in patients diagnosed with Gorlin syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), where almost diagnosed with Gorlin syndrome, or nevoid basal cell carcinoma syndrome (NBCCS), where almost all all cases are characterized by PTCH1 loss of heterozygosity, leading to ligand-independent constitutive cases are characterized by PTCH1 loss of heterozygosity, leading to ligand-independent constitutive Hh
Summary
Cancer is a term encompassing a broad spectrum of disease uniformly defined by uncontrolled growth and underpinned by genomic instability, leading to further genetic diversity and intratumoural cellular and functional heterogeneity. The cellular mechanisms that regulate CSC maintenance are poorly understood, mounting evidence has implicated key developmental signaling pathways, including Hedgehog, Wnt and Notch, whose roles in regulating embryonic and adult stem and progenitor cells are better defined [6]. Together with a major role in maintaining the self-renewing capacity of adult somatic stem cells [10,11], it is not surprising that the Hh signaling has been widely implicated in CSC function and maintenance. This review focuses on the evidence that exists in favour of the CSC model, the role of the Hedgehog pathway in CSCs in a variety of haematological malignancies and solid tumours, and highlights the strategies that hold the potential to block many aspects of transformation attributed to the CSC phenotype, through inhibition of the Hh signaling pathway
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