Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0699790 (
colon cancer
)
28,837
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cancer chemoresistance is often attributed to the presence of cancer stem cell (CSC)-like cells, but whether they are homogeneously chemoresistant remains unclear. We previously showed that in colon tumors, a subpopulation of
LGR5
+
CSC-like cells driven by TCF1 (TCF7), a Wnt-responsive transcription factor, were responsible for tumorigenicity. Here we demonstrate that the tumorigenic subpopulation of mouse
LGR5
+
cells exists in a slow-cycling state and identify a unique 22-gene signature that characterizes these slow-cycling CSC. Seven of the signature genes are specifically expressed in slow-cycling
LGR5
+
cells from xenografted human colon tumors and are upregulated in
colon cancer
clinical specimens. Among these seven, four genes (
APCDD1,
NOTUM
, PROX1
, and
SP5
) are known to be direct Wnt target genes, and
PROX1
was expressed in the invasive fronts of colon tumors.
PROX1
was activated by TCF1 to induce CDKN1C and maintain a slow-cycling state in
colon cancer
organoids. Strikingly, PROX1 was required for recurrent growth after chemotherapeutic treatment, suggesting that inhibition of slow-cycling CSC by targeting the TCF1-PROX1-CDKN1C pathway is an effective strategy to combat refractory
colon cancer
in combination with conventional chemotherapy. SIGNIFICANCE: These findings illustrate the importance of a slow-cycling CSC subpopulation in
colon cancer
development and chemoresistance, with potential implications for the identified slow-cycling CSC signatures and the TCF1-PROX1-CDKN1C pathway as therapeutic targets.
...
PMID:Slow-Cycling Cancer Stem Cells Regulate Progression and Chemoresistance in Colon Cancer. 3281 13
