The ‘Stem’ Of Cancer Chemoresistance- Targeting Cancer Stem Cells via the Wnt-Beta Catenin Pathway
Sudha Warrier, Associate Professor, Manipal Institute of Regenerative Medicine
Cancer stem
cells (CSCs) are hypothesized to be the pathological counterpart of normal somatic
tissue stem cells. The CSC model proposes that tumours are organ¬ised
hierarchically with a subset of tumour cells at their apex, which possess
self-renewal and multilineage differentiation potential. Cancer stem cells,
unlike the bulk of the cells within the tumor, are elusive to drug treatment
and are unaffected on chemo and radiotherapy. These self-renewing cells are
responsible for the flare up of cancer and remission long after treatment.
Cancer stem cells have a capacity for unlimited self-renewal, as well as the
ability to initiate and drive tumor progression in an animal model. Activated
Wnt/ß-Catenin signaling is a key feature of epithelial cancers and is critical
for metastasis and epithelial-mesenchymal transition (EMT) , a signature trait
of CSCs. We explored the effect of the Wnt antagonist, secreted EMT in CSCs in
gliomas. We found that sFRP4 chemo-sensitizes GSC-enriched cells to commonly
used drugs, by the reversal of EMT and by decreasing drug effluxers. sFRP4 acts
through the Wnt- ß-Catenin pand the Wnt- calcium pathways in inhibiting CSCs.
These findings could be exploited for designing better targeted strategies to
improve chemo-response and eventually eliminate glioblastoma CSCs.
|
|