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 J Briegel; Pablo A Bejarano; Ethan Dmitrovsky; Anthony J Capobianco; David J Robbins

doi:10.1158/0008-5472.CAN-10-2313

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Hedgehog-Producing Cancer Cells Respond to and Require Autocrine Hedgehog Activity

Journal article

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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, …

Cancer research (Chicago, Ill.), Vol.71(13), pp.4454-4463

2011-07-01

DOI: https://doi.org/10.1158/0008-5472.CAN-10-2313

PMCID: PMC3809996

PMID: 21565978

Abstract

Hedgehog

cancer

non-small cell lung carcinoma (NSCLC)

autocrine

A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anti-cancer 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.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.108 Molecular & Cell Biology - Cancer & Development; 1.108.1856 Hedgehog
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: Hedgehog-Producing Cancer Cells Respond to and Require Autocrine Hedgehog Activity
Creators: Samer Singh - Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136
Zhiqiang Wang - Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136
Dennis Liang Fei - Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136
Kendall E Black - Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136
John A Goetz - Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755
Robert Tokhunts - Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136
Camilla Giambelli - Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136
Jezabel Rodriguez-Blanco - Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136
Jun Long - Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136
Ethan Lee - Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232
Karoline J Briegel - Sylvester Cancer Center, Miller School of Medicine, University of Miami, Miami, FL-33136
Pablo A Bejarano - Department of Pathology, Jackson Memorial Hospital, University of Miami, Miami, Florida 33136
Ethan Dmitrovsky - Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755
Anthony J Capobianco - Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136
David J Robbins - Molecular Oncology Program, Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136
Publication Details: Cancer research (Chicago, Ill.), Vol.71(13), pp.4454-4463
Academic Unit: Miller School of Medicine; UMMG Department of Surgery; UMMG Dept of Surgery - Div of Surgical Oncology
Language: English
Resource Type: Journal article
PMID: 21565978
PMCID: PMC3809996
Record Identifier: 991031559876202976