Heat shock proteins in cancer stem cell maintenance: a potential therapeutic target?
2020
Cancer stem cells (CSCs) are a
subpopulation of tumor cells with unlimited self-renewal
capability, multilineage differentiation potential and
long-term tumor repopulation capacity. CSCs reside in
anatomically distinct regions within the tumor
microenvironment, called niches, and this favors the
maintenance of CSC properties and preserves their
phenotypic plasticity. Indeed, CSCs are characterized by
a flexible state based on their capacity to interconvert
between a differentiated and a stem-like phenotype, and
this depends on the activation of adaptive mechanisms in
response to different environmental conditions. Heat
Shock Proteins (HSPs) are molecular chaperones,
upregulated upon cell exposure to several stress
conditions and are responsible for normal maturation,
localization and activity of intra and extracellular
proteins. Noteworthy, HSPs play a central role in several
cellular processes involved in tumor initiation and
progression (i.e. cell viability, resistance to apoptosis,
stress conditions and drug therapy, EpithelialMesenchymal Transition (EMT), bioenergetics,
invasiveness, metastasis formation) and, thus, are widely
considered potential molecular targets. Furthermore,
much evidence suggests a key regulatory function for
HSPs in CSC maintenance and their upregulation has
been proposed as a mechanism used by CSCs to adapt to
unfavorable environmental conditions, such as nutrient
deprivation, hypoxia, inflammation. This review
discusses the relevance of HSPs in CSC biology,
highlighting their role as novel potential molecular
targets to develop anticancer strategies aimed at CSC
targeting.
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