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2015 ; 8
(4
): 385-91
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gab.com Text
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Downregulation of Wnt signaling by sonic hedgehog activation promotes
repopulation of human tumor cell lines
#MMPMID25713298
Ma J
; Cheng J
; Gong Y
; Tian L
; Huang Q
Dis Model Mech
2015[Apr]; 8
(4
): 385-91
PMID25713298
show ga
Tumor repopulation after radiotherapy is a big obstacle for clinical cancer
therapy. The molecular mechanisms of tumor cell repopulation after radiotherapy
remain unclear. This study investigated the role of sonic hedgehog (SHH) and Wnt
signaling pathways in tumor repopulation after radiotherapy in an in vitro
repopulation model. In this model, irradiated dying tumor cells functioned as
feeder cells, whereas luciferase-labeled living tumor cells acted as reporter
cells. Proliferation of reporter cells was measured by bioluminescence imaging.
Results showed that irradiated dying HT29 and Panc1 tumor cells significantly
stimulated the repopulation of living cells in their respective cultures. In HT29
and Panc1 cells, radiation significantly inhibited Wnt activity. In the
irradiated dying HT29 and Panc1 cells, the level of the activated nuclear
?-catenin was significantly decreased. Treatment with the Wnt agonist 68166
significantly decreased, whereas treatment with Wnt antagonist significantly
increased, repopulation in HT29 and Panc1 tumor cells in a dose-dependent manner.
?-catenin short-hairpin RNA (shRNA) also significantly promoted tumor cell
repopulation. The level of secreted frizzled related protein-1 (SFRP1), hedgehog
and Gli1 were increased in irradiated cells. Our results highlight the
interaction between Wnt and SHH signaling pathways in dying tumor cells and
suggest that downregulation of Wnt signaling after SHH activation is negatively
associated with tumor repopulation.