Hedgehog signaling pathway for advanced ovarian cancer: cross-talk mTOR/AKT kinase

AJBM crossMark

Yingying Yang¹, Yujie Han, Yongbo Zuo, Dandan Wang, Lina Huang, Jing Ben, Ning Lu∗

Ovarian cancer is the most common cause of cancer death from gynecologic tumors in the United States. Hedgehog (Hh) signaling plays important roles in embryonic development and in tumor formation. Hh ligands promote the phosphorylation and activation of mTOR and AKT kinases, yet the molecular mechanism underlying these processes are unknown. In the present study, we assessed the effects of Hh on human Ovarian cancer cells, and discussed Hh inhibition therapeutic mechanism involving hedgehog signaling-related proteins. This study provides an experimental basis for a better understanding of Res molecular mechanisms, better treatment outcomes, and increases survival rates as an anticancer agent. Hh signaling induces activation of the mTOR/AKT kinase signaling arm, resulting in up-regulation of human ovarian cancer cells. We concluded that targeting the hedgehog pathway offers a novel treatment approach for advance ovarian cancer.

Keywords: Ovarian cancer; Hedgehog; mTOR; AKT kinase

Copyright © 2016 by The American Society for BioMedicine and BM-Publisher, Inc.

Article citationReferencesFull-Text/PDFFeedback
The citation data is computed by the following citation measuring services:

Google scholarcitedby


  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J. Clin 201666:7-30. [Wiley Online Library]
  2. Chornokur G, Amankwah EK, Schildkraut JM, Phelan CM. Global ovarian cancer health disparities. Gynecol Oncol 2013;129:258–264. [CrossRef]
  3.  Pallag A, Rosca E, ţiŢ DM, MuŢiu G, Bungău SG, Pop OL. Monitoring the effects of treatment in colon cancer cells using immunohistochemical and histoenzymatic techniques. Rom J Morphol Embryol 2015;56:1103–1109. [PubMed]
  4. Briscoe J, Thérond PP. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol 2013;1:416–429. [PubMed]
  5. Jia Y, Wang Y, Xie J. The Hedgehog pathway: role in cell differentiation, polarity and proliferation. Arch Toxicol 2015;89:179–191. [PMC free article] [PubMed]
  6. Stecca B, Ruiz I, Altaba A. Context-dependent regulation of the GLI code in cancer by Hedgehog and non-Hedgehog signals. J Mol Cell Biol 2010;2:84–95. [PMC free article] [PubMed]
  7. Onishi H, Katano M. Hedgehog signaling pathway as a therapeutic target in various types of cancer. Cancer Sci 2011;102:1756–1760. [PubMed]
  8. Key TJ. Fruit and vegetables and cancer risk. Br J Cancer 2011;104:6–11. [PMC free article] [PubMed]
  9.  Frazzi R, Valli R, Tamagnini I, Casali B, Latruffe N, Merli F. Resveratrol- mediated apoptosis of hodgkin lymphoma cells involves SIRT1 inhibition and FOXO3a hyperacetylation. Int J Cancer 2013;132:1013–1021. [PubMed]
  10. Xie J, Bartels CM, Barton SW, Gu D. Targeting hedgehog signaling in cancer: research and clinical developments. Onco Targets Ther 2013;6:1425–1435.[PubMed]
  11. Von Hoff DD, LoRusso PM, Rudin CM, et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 2009;361:1164–1172. [PubMed]
  12. Yang L, Xie G, Fan Q, Xie J. Activation of the hedgehog-signaling pathway in human cancer and the clinical implications. Oncogene 2010;29:469–481. [PubMed]
  13. Gu D, Liu H, Su GH, et al. Combining hedgehog signaling inhibition with focal irradiation on reduction of pancreatic cancer metastasis. Mol Cancer Ther 2013;12:1038–1048. [PMC free article] [PubMed]
  14.  Hwang RF, Moore TT, Hattersley MM, et al. Inhibition of the hedgehog pathway targets the tumor-associated stroma in pancreatic cancer. Mol Cancer Res 2012;10:1147–1157. [PMC free article] [PubMed]
  15. Khan A, Aljarbou AN, Aldebasi YH, Faisal SM, Khan MA. Resveratrol suppresses the proliferation of breast cancer cells by inhibiting fatty acid synthase signaling pathway. Cancer Epidemiol 2014;38:765–772. [PubMed]
  16.  Aggarwal BB, Bhardwaj A, Aggarwal RS, Seeram NP, Shishodia S, Takada Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res 2004;24:2783–840. [PubMed]
  17. Joost S, Almada LL, Rohnalter V, et al. GLI1 inhibition promotes epithelial-to-mesenchymal transition in pancreatic cancer cells. Cancer Res 2012;72:88–99. [PMC free article] [PubMed]
  18. Echelard Y, Epstein DJ, St-Jacques B, et al. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell 1993;75(7):1417–1430. [PubMed]
  19.  Riddle RD, Johnson RL, Laufer E, Tabin C. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell. 1993;75(7):1401–1416. [PubMed]
  20. Xie J. Hedgehog signaling pathway: development of antagonists for cancer therapy. Curr Oncol Rep 2008;10(2):107–113. [PubMed]
  21.  Jiang J, Hui CC. Hedgehog signaling in development and cancer. Dev Cell 2008;15(6):801–812. [PubMed]
  22. Ingham PW, Placzek M. Orchestrating ontogenesis: variations on a theme by sonic hedgehog. Nat Rev Genet 2006;7(11):841–850. [PubMed]
  23. McMahon AP, Ingham PW, Tabin CJ. Developmental roles and clinical significance of hedgehog signaling. Curr Top Dev Biol 2003;53:1–114. [PubMed]
  24. Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev 2001;15(23):3059–3087. [PubMed]
  25. Porter JA, von Kessler DP, Ekker SC, et al. The product of hedgehog autoproteolytic cleavage active in local and long-range signalling. Nature. 1995;374(6520):363–366. [PubMed]
  26. Kawakami T, Kawcak T, Li YJ, Zhang W, Hu Y, Chuang PT. Mouse dispatched mutants fail to distribute hedgehog proteins and are defective in hedgehog signaling. Development 2002;129(24):5753–5765. [PubMed]
  27. Stone DM, Hynes M, Armanini M, et al. The tumour-suppressor gene patched encodes a candidate receptor for sonic hedgehog. Nature 1996;384(6605):129–134. [PubMed]
  28.   Chuang PT, McMahon AP. Vertebrate hedgehog signalling modulated by induction of a hedgehog-binding protein. Nature 1999;397(6720):617–621. [PubMed]


1. Access this article through OpenAthens

2. Access this article through your login credentials/Subscription

Get Access

3. Purchase this article at rate $55.00 and received Full-Text/PDF
You will have online immediate access to article following the completion of this purchase and you may download and print a copy of each article for your personal use. Use the coding below to purchase your article as PDF by credit card, debit card, will be asked to supply your billing card information. Before continue with your purchase please read carefully the BM-Publisher terms and conditions of purchase.

Purchase Article

For any technique error please contact us and will be response to sending purchase article by email.

Who Can Become a Reviewer?
Any expert in the article's research field can become a reviewer with American Journal of Biomedicine. Editors might ask you to look at a specific aspect of an article,...

Find out more

Thank you for visiting American Journal of BioMedicine. * = Required fields

Error: Contact form not found.

Print Friendly, PDF & Email

DOI: 10.18081/2333-5106/016-11/505-512

Cited by in Scopus

Research Article
American Journal of BioMedicine Volume 4, Issue 11, pages 505-512
Received June 01, 2016; accepted October 30, 2016; published November 28, 2016

How to cite this article
Yang Y, Han Y, Zuo Y, et al. Hedgehog signaling pathway for advanced ovarian cancer: cross-talk mTOR/AKT kinase. American Journal of BioMedicine 2016;4(11):505-512.

Article outline
1. Abstract
2. Keywords
3. Introduction
4. Materials and Methods
5. Results
6. Discussions
7. Acknowledgements
8. References