Most human cancers derive from a single cell targeted
by genetic and epigenetic alterations that initiate
malignant transformation. Progressively, these
early cancer cells give rise to different generations
of daughter cells that accumulate additional mutations,
acting in concert to drive the full neoplastic
phenotype1,2. As we have currently deciphered
many of the gene pathways disrupted in cancer, our
knowledge about the nature of the normal cells
susceptible to transformation upon mutation has
remained more elusive.
Adult stem cells are those that show long-term
replicative potential, together with the capacities of
self-renewal and multi-lineage differentiation. These
stem cell properties are tightly regulated in normal
development, yet their alteration may be a critical
issue for tumorigenesis. This concept has arisen
from the striking degree of similarity noted between
somatic stem cells and cancer cells, including
the fundamental abilities to self-renew and differentiate.
Given these shared attributes, it has been
proposed that cancers are caused by transforming
mutations occurring in tissue-specific stem cells3-9.
This hypothesis has been functionally supported by
the observation that among all cancer cells within a
particular tumor, only a minute cell fraction has the
exclusive potential to regenerate the entire tumor
cell population3,10-13; these cells with stem-like
properties have been termed cancer stem cells.
Cancer stem cells can originate from mutation in
normal somatic stem cells that deregulate their
physiological programs. Alternatively, mutations
may target more committed progenitor cells or
even mature cells, which become reprogrammed to
acquire stem-like functions14,15 In any case, mutated
genes should promote expansion of stem/progenitor
cells, thus increasing their predisposition to
cancer development by expanding self-renewal and
pluripotency over their normal tendency towards
relative quiescency and proper differentiation.