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Target Concepts:
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Query: UMLS:C0019204 (
hepatocellular carcinoma
)
71,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Various populations of cancer stem cells (CSCs) have been identified in
hepatocellular carcinoma
(
HCC
). Wnt signaling is variably activated in
HCC
and regulates CSCs and tumorigenesis. We explored cell-to-cell Wnt and stemness heterogeneity in
HCC
by labeling freshly isolated cancer cells with a Wnt-specific reporter, thereby identifying a small subset (0.4%-8.9%) of Wnt-activity
high
cells. Further cellular subset analysis identified a refined subset of Wnt-activity
high
ALDH1
+
EpCAM
+
triple-positive (TP) cells as the most stem-like, phenotypically plastic, and tumorigenic among all putative CSC populations. These TP "superpotent CSCs" (spCSCs) specifically upregulate the expression of
dishevelled 1
(
DVL1
) through the antagonism between abnormal spindle-like microcephaly-associated (ASPM) and the ubiquitin ligase complex Cullin-3/KLHL-12. Subsequent functional and molecular studies revealed the role of
DVL1
in controlling spCSCs and their tumorigenic potential. These findings provide the mechanistic basis of the Wnt and stemness heterogeneity in
HCC
and highlight the important role of
DVL1
high
spCSCs in tumor progression.
...
PMID:Dishevelled 1-Regulated Superpotent Cancer Stem Cells Mediate Wnt Heterogeneity and Tumor Progression in Hepatocellular Carcinoma. 3216 May 21
