A crucial requirement for Hedgehog signaling in small cell lung cancer (original) (raw)

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Acknowledgements

We would like to thank A. Berns (The Netherlands Cancer Institute) and M. Scott (Stanford University) for the _Trp53_lox and Ptch1 lacZ/+ mice, respectively, J. Whitsett (Cincinnati Children's Hospital) for the antibodies to surfactant protein C, C. Janke (Orsay Curie Institute) for antibodies to polyglutamylated tubulin and C.-M. Fan (Carnegie Institution of Washington) for the adenovirally expressed SmoM2 virus, as well as T. Oro, James Kim, Jynho Kim and P. Beachy for helpful discussions throughout the course of this study. We thank R. Toftgård (Karolinska Institute) and K. McGovern at Infinity Pharmaceuticals for their generous gift of the GANT-61 and cyclopamine, respectively, R. Rohatgi for help with the immunoblot analysis and B. Schaffer for help with the cell culture. This work was supported by the Lucile Packard Foundation for Children's Health (J.S.), the Damon Runyon Cancer Research Foundation (J.S.), the American Lung Association (J.S. and K.-S.P.), the Francis Family Foundation (K.-S.P.), the American Cancer Society (J.S.), the Tobacco-Related Disease Research Program of California (J.F.C.), US National Institutes of Health (NIH) National Cancer Institute R01 CA136574 (J.K.C.), the Flight Attendant Medical Research Institute (YCSA 072033) (C.D.P.), NIH 5T32 CA009302-33 (C.O.), the National Health and Medical Research Council of Australia project grants 546024 and 546098 and the Victorian Cancer Agency (D.N.W., L.G.M. and A.S.), the Deutsche Krebshilfe (107954) (R.K.T.), the German Ministry of Science and Education as part of the Nationales Genomforschungsnetz (NGFN-plus) program (01GS08100) (R.K.T.), the Max Planck Society (MIFA NEUR8061) (R.K.T.), the Deutsche Forschungsgemeinschaft (DFG) through Sonderforschungsbereiche (TP6) (R.K.T.), the Ministry for Innovation, Science, Research and Technology of the State of Nordrhein-Westfalen (MIWT, 4000-12 09) (R.K.T.) and by an anonymous foundation to R.K.T.

Author information

Author notes

1. Kwon-Sik Park, Luciano G Martelotto, Craig D Peacock and Julien Sage: These authors contributed equally to this work.

Authors and Affiliations

1. Department of Pediatrics, Stanford University, Stanford, California, USA
   Kwon-Sik Park, Katie Bernard, Jamie F Conklin & Julien Sage
2. Department of Genetics, Stanford University, Stanford, California, USA
   Kwon-Sik Park, Moe R Mahjoub, Katie Bernard, Jamie F Conklin, Tim Stearns & Julien Sage
3. Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia
   Luciano G Martelotto, Anette Szczepny & D Neil Watkins
4. Max Planck Institute for Neurological Research with Klaus-Joachim-Zülch Laboratories of the Max Planck Society and the Medical Faculty of the University of Cologne, University of Cologne, Cologne, Germany
   Martin Peifer, Martin L Sos & Roman K Thomas
5. Department of Internal Medicine and Center of Integrated Oncology Köln-Bonn, University of Cologne, Cologne, Germany
   Martin L Sos & Roman K Thomas
6. University of California–San Francisco Department of Pathology, San Francisco, California, USA
   Anthony N Karnezis
7. Department of Biology, Stanford University, Stanford, California, USA
   Moe R Mahjoub & Tim Stearns
8. Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
   Jing Yuan, Ribo Guo, Beatrice Ospina, Marion Dorsch & Silvia Buonamici
9. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
   Jeanette Falzon, Samara Bennett & Tracey J Brown
10. Sidney Kimmel Cancer Centre, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Ana Markovic, Wendy L Devereux & Craig D Peacock
11. Department of Chemical and Systems Biology, Stanford University, Stanford, California, USA
    Cory A Ocasio & James K Chen
12. Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Köln-Bonn, University of Cologne, Cologne, Germany
    Roman K Thomas

Authors

1. Kwon-Sik Park
2. Luciano G Martelotto
3. Martin Peifer
4. Martin L Sos
5. Anthony N Karnezis
6. Moe R Mahjoub
7. Katie Bernard
8. Jamie F Conklin
9. Anette Szczepny
10. Jing Yuan
11. Ribo Guo
12. Beatrice Ospina
13. Jeanette Falzon
14. Samara Bennett
15. Tracey J Brown
16. Ana Markovic
17. Wendy L Devereux
18. Cory A Ocasio
19. James K Chen
20. Tim Stearns
21. Roman K Thomas
22. Marion Dorsch
23. Silvia Buonamici
24. D Neil Watkins
25. Craig D Peacock
26. Julien Sage

Contributions

A.N.K. analyzed the histopathology of all mouse lung tumors and edited the manuscript. A.S. performed and analyzed the immunohistochemistry. D.N.W. and L.G.M. edited the manuscript and analyzed the immunohistochemistry. L.G.M. performed experiments with Smo inhibitors and chemotherapy in culture and in xenografts. C.A.O. and J.K.C. generated HPI-1 for cell culture experiments. J.K.C. edited the manuscript. M.R.M. and T.S. designed, performed and analyzed the experiments related to the primary cilia in mouse cells. M.P., M.L.S. and R.K.T. designed and performed the experiments related to the genomic analysis of mouse and human tumors. K.-S.P. and K.B. quantified the proliferation and survival phenotypes in tumors treated with cyclopamine. K.-S.P. and J.F.C. analyzed gene and protein expression levels in tumor cells. K.-S.P. performed all the other experiments involving mouse cells. K.-S.P. and J.S. designed the experiments for the analysis of mouse SCLC cells in culture and in vivo, and generated the corresponding figures. C.D.P. designed and analyzed the research performed by A.M. and W.L.D. on the human SCLC cells in vitro. J.F., S.Buonamici, S. Bennett, J.Y., R.G., B.O., M.D., A.M., W.L.D. and T.J.B. designed and performed in vivo xenograft experiments and analyzed the data. K.-S.P., J.S., C.D.P. and S.B. wrote and edited the manuscript.

Corresponding authors

Correspondence toCraig D Peacock or Julien Sage.

Ethics declarations

Competing interests

D.N.W. is a co-inventor on a patent application for the use of Smo antagonists in SCLC. J.K.C. has consulted for Fate Therapeutics, and J.S. has consulted for Infinity Pharmaceuticals. R.K.T. received consulting and lecture fees (from Sequenom, Sanofi-Aventis, Merck, Roche, Infinity, Boehringer, AstraZeneca and ATLAS Biolabs) as well as research support (from Novartis and AstraZeneca). S.B., J.Y., B.O. and R.G. are employees of Novartis Institute of BioMedical Research. M.D. is an employee of Sanofi-aventis.

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Supplementary Discussion, Supplementary Methods, Supplementary Figures 1–8 and Supplementary Tables 1 and 2 (PDF 1786 kb)

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Park, KS., Martelotto, L., Peifer, M. et al. A crucial requirement for Hedgehog signaling in small cell lung cancer.Nat Med 17, 1504–1508 (2011). https://doi.org/10.1038/nm.2473

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• Received: 06 September 2010
• Accepted: 16 August 2011
• Published: 09 October 2011
• Issue date: November 2011
• DOI: https://doi.org/10.1038/nm.2473