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Epigenetic regulation of mammalian Hedgehog signaling to the stroma determines the molecular subtype of bladder cancer

Title
Epigenetic regulation of mammalian Hedgehog signaling to the stroma determines the molecular subtype of bladder cancer
Authors
KIM, SANGUKShin, Kunyoo
Date Issued
30-Apr-2019
Publisher
ELIFE SCIENCES PUBLICATIONS LTD
Abstract
In bladder, loss of mammalian Sonic Hedgehog (Shh) accompanies progression to invasive urothelial carcinoma, but the molecular mechanisms underlying this cancer-initiating event are poorly defined. Here, we show that loss of Shh results from hypermethylation of the CpG shore of the Shh gene, and that inhibition of DNA methylation increases Shh expression to halt the initiation of murine urothelial carcinoma at the early stage of progression. In full-fledged tumors, pharmacologic augmentation of Hedgehog (Hh) pathway activity impedes tumor growth, and this cancer-restraining effect of Hh signaling is mediated by the stromal response to Shh signals, which stimulates subtype conversion of basal to luminal-like urothelial carcinoma. Our findings thus provide a basis to develop subtype-specific strategies for the management of human bladder cancer.
Keywords
CELL-LINE; URINARY-BLADDER; COLON-CANCER; MOUSE MODEL; STEM-CELLS; TUMOR; EXPRESSION; MUSCLE; CARCINOMA; EFFICACY
URI
http://oasis.postech.ac.kr/handle/2014.oak/99356
ISSN
2050-084X
Article Type
Article
Citation
ELIFE, vol. 8, 2019-04-30
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 KIM, SANGUK
Dept of Life Sciences
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