Hedgehog-producing cancer cells respond to and require autocrine hedgehog activity

Samer Singh, Zhiqiang Wang, Dennis Liang Fei, Kendall E. Black, John A. Goetz, Robert Tokhunts, Camilla Giambelli, Jezabel Rodriguez-Blanco, Jun Long, Ethan Lee, Karoline Briegel, Pablo A. Bejarano, Ethan Dmitrovsky, Anthony J Capobianco, David J Robbins

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anticancer agents. These drugs are proposed to attenuate tumor growth solely through inhibition of Hedgehog (HH), which is produced in tumor cells but acts on tumor stromal cells. The pivotal argument underlying this model is that the growth-inhibitory properties of SMO antagonists on HH-producing cancer cells are due to their off-target effects. Here, we show that the tumorigenic properties of such lung cancer cells depend on their intrinsic level of HH activity. Notably, reducing HH signaling in these tumor cells decreases HH target gene expression. Taken together, these results question the dogma that autocrine HH signaling plays no role in HH-dependent cancers, and does so without using SMO antagonists.

Original languageEnglish
Pages (from-to)4454-4463
Number of pages10
JournalCancer Research
Volume71
Issue number13
DOIs
StatePublished - Jul 1 2011

Fingerprint

Neoplasms
Autocrine Communication
Stromal Cells
Growth
Antineoplastic Agents
Lung Neoplasms
Clinical Trials
Gene Expression
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hedgehog-producing cancer cells respond to and require autocrine hedgehog activity. / Singh, Samer; Wang, Zhiqiang; Fei, Dennis Liang; Black, Kendall E.; Goetz, John A.; Tokhunts, Robert; Giambelli, Camilla; Rodriguez-Blanco, Jezabel; Long, Jun; Lee, Ethan; Briegel, Karoline; Bejarano, Pablo A.; Dmitrovsky, Ethan; Capobianco, Anthony J; Robbins, David J.

In: Cancer Research, Vol. 71, No. 13, 01.07.2011, p. 4454-4463.

Research output: Contribution to journalArticle

Singh, S, Wang, Z, Fei, DL, Black, KE, Goetz, JA, Tokhunts, R, Giambelli, C, Rodriguez-Blanco, J, Long, J, Lee, E, Briegel, K, Bejarano, PA, Dmitrovsky, E, Capobianco, AJ & Robbins, DJ 2011, 'Hedgehog-producing cancer cells respond to and require autocrine hedgehog activity', Cancer Research, vol. 71, no. 13, pp. 4454-4463. https://doi.org/10.1158/0008-5472.CAN-10-2313
Singh S, Wang Z, Fei DL, Black KE, Goetz JA, Tokhunts R et al. Hedgehog-producing cancer cells respond to and require autocrine hedgehog activity. Cancer Research. 2011 Jul 1;71(13):4454-4463. https://doi.org/10.1158/0008-5472.CAN-10-2313
Singh, Samer ; Wang, Zhiqiang ; Fei, Dennis Liang ; Black, Kendall E. ; Goetz, John A. ; Tokhunts, Robert ; Giambelli, Camilla ; Rodriguez-Blanco, Jezabel ; Long, Jun ; Lee, Ethan ; Briegel, Karoline ; Bejarano, Pablo A. ; Dmitrovsky, Ethan ; Capobianco, Anthony J ; Robbins, David J. / Hedgehog-producing cancer cells respond to and require autocrine hedgehog activity. In: Cancer Research. 2011 ; Vol. 71, No. 13. pp. 4454-4463.
@article{2400ff14a6e34e89bba09d059d4a0053,
title = "Hedgehog-producing cancer cells respond to and require autocrine hedgehog activity",
abstract = "A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anticancer agents. These drugs are proposed to attenuate tumor growth solely through inhibition of Hedgehog (HH), which is produced in tumor cells but acts on tumor stromal cells. The pivotal argument underlying this model is that the growth-inhibitory properties of SMO antagonists on HH-producing cancer cells are due to their off-target effects. Here, we show that the tumorigenic properties of such lung cancer cells depend on their intrinsic level of HH activity. Notably, reducing HH signaling in these tumor cells decreases HH target gene expression. Taken together, these results question the dogma that autocrine HH signaling plays no role in HH-dependent cancers, and does so without using SMO antagonists.",
author = "Samer Singh and Zhiqiang Wang and Fei, {Dennis Liang} and Black, {Kendall E.} and Goetz, {John A.} and Robert Tokhunts and Camilla Giambelli and Jezabel Rodriguez-Blanco and Jun Long and Ethan Lee and Karoline Briegel and Bejarano, {Pablo A.} and Ethan Dmitrovsky and Capobianco, {Anthony J} and Robbins, {David J}",
year = "2011",
month = "7",
day = "1",
doi = "10.1158/0008-5472.CAN-10-2313",
language = "English",
volume = "71",
pages = "4454--4463",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "13",

}

TY - JOUR

T1 - Hedgehog-producing cancer cells respond to and require autocrine hedgehog activity

AU - Singh, Samer

AU - Wang, Zhiqiang

AU - Fei, Dennis Liang

AU - Black, Kendall E.

AU - Goetz, John A.

AU - Tokhunts, Robert

AU - Giambelli, Camilla

AU - Rodriguez-Blanco, Jezabel

AU - Long, Jun

AU - Lee, Ethan

AU - Briegel, Karoline

AU - Bejarano, Pablo A.

AU - Dmitrovsky, Ethan

AU - Capobianco, Anthony J

AU - Robbins, David J

PY - 2011/7/1

Y1 - 2011/7/1

N2 - A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anticancer agents. These drugs are proposed to attenuate tumor growth solely through inhibition of Hedgehog (HH), which is produced in tumor cells but acts on tumor stromal cells. The pivotal argument underlying this model is that the growth-inhibitory properties of SMO antagonists on HH-producing cancer cells are due to their off-target effects. Here, we show that the tumorigenic properties of such lung cancer cells depend on their intrinsic level of HH activity. Notably, reducing HH signaling in these tumor cells decreases HH target gene expression. Taken together, these results question the dogma that autocrine HH signaling plays no role in HH-dependent cancers, and does so without using SMO antagonists.

AB - A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anticancer agents. These drugs are proposed to attenuate tumor growth solely through inhibition of Hedgehog (HH), which is produced in tumor cells but acts on tumor stromal cells. The pivotal argument underlying this model is that the growth-inhibitory properties of SMO antagonists on HH-producing cancer cells are due to their off-target effects. Here, we show that the tumorigenic properties of such lung cancer cells depend on their intrinsic level of HH activity. Notably, reducing HH signaling in these tumor cells decreases HH target gene expression. Taken together, these results question the dogma that autocrine HH signaling plays no role in HH-dependent cancers, and does so without using SMO antagonists.

UR - http://www.scopus.com/inward/record.url?scp=79959885131&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959885131&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-10-2313

DO - 10.1158/0008-5472.CAN-10-2313

M3 - Article

VL - 71

SP - 4454

EP - 4463

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 13

ER -