Evidence base and patients' perspective - World Journal of ...

experiments and preclinical and clinical trials. Nigericin
may prove to be the therapeutic strategy that is effective
in patients with metastatic disease.
However, the molecular mechanisms involved in the
effect of nigericin are poorly understood. Lu et al [13] have
reported that nigericin, as a potassium ionophore, selectively
inhibits Wnt1-mediated signaling in HEK293 cells.
The polyether ionophores like nigericin interfere with
transmembrane potassium potential and promote mitochondrial
and cell potassium efflux. We hypothesize that
nigericin treatment antagonizes the Wnt signaling cascade,
while Wnt signaling plays a crucial role in embryonic
development and cancer [31-35] . Besides, certain other CSC
markers and signaling pathways, including EZH2 and
Hedgehog pathways may also play some important roles
in the mechanism of nigericin treatment, and thus need
further studies [36] . Further studies will focus on the relation
between nigericin-induced EMT and Wnt signaling.
We showed for the first time that nigericin not only
partly reversed the EMT process during cell invasion and
metastasis, but also suppressed some of the CSC phenotypes
generated by EMT. EMT plays a pivotal role in
tumor invasion and metastasis; therefore, nigericin treatment
may be of benefit in the future.
ACKNOWLEDGMENTS
We thank Pei-Qin Yu, Xue-Hua Chen for their technical
assistance, and also thank the members of Shanghai
Institute of Digestive Surgery, Shanghai for useful advice
and guidance.
COMMENTS
Background
Despite therapeutic innovations, metastatic colorectal cancer (CRC) often has a
poor prognosis and high mortality.
Research frontiers
Epithelial-mesenchymal transition (EMT) provides a new basis for understanding
the progression of carcinoma towards dedifferentiated and more malignant
states. The EMT program, which involves dissolution of adherens and tight
junctions and a loss of cell polarity, dissociates the cells with epithelial cell
sheets into individual cells that exhibit multiple mesenchymal attributes, including
heightened invasiveness. EMT also generates cells with properties of stem
cells. Nigericin has been reported recently to act as a selective breast cancer
stem cell inhibitor. However, the effect of nigericin on CRC is unknown. In this
study, the authors evaluated the anticancer effect of nigericin and its possible
mechanisms.
Innovations and breakthroughs
Recent reports have highlighted the important role of EMT during the invasionmetastasis
cascade. In particular, EMT can be seen at the edges of colon carcinomas
that are invading adjacent tissues. This is the first study to report that
nigericin could suppress CRC metastasis. Furthermore, our studies indicated
the possible mechanisms of action of nigericin.
Applications
Through understanding the effect of nigericin on CRC cells, this study may
indicate a future promising therapeutic strategy in the treatment of patients with
metastatic colorectal carcinoma.
Terminology
E-cadherin is a hallmark of epithelial cell protein expression; vimentin is an
intermediate filament component of the mesenchymal cell cytoskeleton. CD133
protein, a pentaspan cell surface receptor, is a putative CRC stem cell marker.
WJG|www.wjgnet.com
Zhou HM et al �� Nigericin and colorectal cancer
Peer review
The study investigated the antitumor activity of nigericin on CRC stem cells.
The authors found that nigericin selectively targeted cancer stem cells, and
inhibited EMT. It is well designed and well presented.
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