Hedgehog Signaling in the Maintenance of Cancer Stem Cells.
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.
Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia. catherine.cochrane@hudson.org.au.|Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia. catherine.cochrane@hudson.org.au.
Catherine R
CR
Cochrane
Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia. anette.szczepny@hudson.org.au.|Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia. anette.szczepny@hudson.org.au.
Anette
A
Szczepny
The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia. n.watkins@garvan.org.au.|UNSW Faculty of Medicine, Randwick, New South Wales 2031, Australia. n.watkins@garvan.org.au.|Department of Thoracic Medicine, St Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia. n.watkins@garvan.org.au.
D Neil
DN
Watkins
Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia. jason.cain@hudson.org.au.|Department of Molecular and Translational Science, Monash University, Clayton, Victoria 3168, Australia. jason.cain@hudson.org.au.
Jason E
JE
Cain
cancer stem cells; hedgehog signaling; tumourigenesis