Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors

Kunyoo Shin, Agnes Lim, Chen Zhao, Debashis Sahoo, Ying Pan, Edda Spiekerkoetter, Joseph C. Liao, Philip A. Beachy

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Hedgehog (Hh) pathway inhibitors are clinically effective in treatment of basal cell carcinoma and medulloblastoma, but fail therapeutically or accelerate progression in treatment of endodermally derived colon and pancreatic cancers. In bladder, another organ of endodermal origin, we find that despite its initial presence in the cancer cell of origin Sonic hedgehog (Shh) expression is invariably lost during progression to invasive urothelial carcinoma. Genetic blockade of stromal response to Shh furthermore dramatically accelerates progression and decreases survival time. This cancer-restraining effect of Hh pathway activity is associated with stromal expression of BMP signals, which stimulate urothelial differentiation. Progression is dramatically reduced by pharmacological activation of BMP pathway activity with low-dose FK506, suggesting an approach to management of human bladder cancer.

Original languageEnglish (US)
Pages (from-to)521-533
Number of pages13
JournalCancer Cell
Volume26
Issue number4
DOIs
StatePublished - Oct 13 2014

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Urinary Bladder Neoplasms
Medulloblastoma
Basal Cell Carcinoma
Tacrolimus
Pancreatic Neoplasms
Colonic Neoplasms
Neoplasms
Urinary Bladder
Pharmacology
Carcinoma
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology
  • Medicine(all)

Cite this

Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors. / Shin, Kunyoo; Lim, Agnes; Zhao, Chen; Sahoo, Debashis; Pan, Ying; Spiekerkoetter, Edda; Liao, Joseph C.; Beachy, Philip A.

In: Cancer Cell, Vol. 26, No. 4, 13.10.2014, p. 521-533.

Research output: Contribution to journalArticle

Shin, K, Lim, A, Zhao, C, Sahoo, D, Pan, Y, Spiekerkoetter, E, Liao, JC & Beachy, PA 2014, 'Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors', Cancer Cell, vol. 26, no. 4, pp. 521-533. https://doi.org/10.1016/j.ccell.2014.09.001
Shin, Kunyoo ; Lim, Agnes ; Zhao, Chen ; Sahoo, Debashis ; Pan, Ying ; Spiekerkoetter, Edda ; Liao, Joseph C. ; Beachy, Philip A. / Hedgehog signaling restrains bladder cancer progression by eliciting stromal production of urothelial differentiation factors. In: Cancer Cell. 2014 ; Vol. 26, No. 4. pp. 521-533.
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