Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas - PubMed (original) (raw)
. 2005 Oct;26(10):1698-705.
doi: 10.1093/carcin/bgi130. Epub 2005 May 19.
Affiliations
- PMID: 15905200
- DOI: 10.1093/carcin/bgi130
Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas
Xiaoli Ma et al. Carcinogenesis. 2005 Oct.
Abstract
The hedgehog pathway plays a critical role in the development of the foregut. Recent studies indicate that the hedgehog pathway activation occurs in the stomach and other gastrointestinal cancers. However, the association of hedgehog pathway activation with tumor stage, differentiation and tumor subtype is not well documented. Here, we report our findings that the elevated expression of hedgehog target genes human patched gene 1 (PTCH1) or Gli1 occurs in 63 of the 99 primary gastric cancers. Activation of the hedgehog pathway is associated with poorly differentiated and more aggressive tumors. The sonic hedgehog (Shh) transcript is localized to the cancer tissue, whereas expression of Gli1 and PTCH1 is observed both in the cancer and in the surrounding stroma. Treatment of gastric cancer cells with KAAD-cyclopamine, a hedgehog signaling inhibitor, decreases expression of Gli1 and PTCH1, resulting in cell growth inhibition and apoptosis. Overexpression of Gli1 under the control of the cytomegalovirus (CMV) promoter renders these cells resistant to cyclopamine-induced apoptosis. Thus, our analysis of in vivo tissues indicates that the hedgehog pathway is frequently activated in advanced gastric adenocarcinomas; our in vitro studies suggest that hedgehog signaling contributes to gastric cancer cell growth. These data predict that targeted inhibition of the hedgehog pathway may be effective in the prevention and treatment of advanced gastric adenocarcinomas.
Similar articles
- Hedgehog signaling is activated in subsets of esophageal cancers.
Ma X, Sheng T, Zhang Y, Zhang X, He J, Huang S, Chen K, Sultz J, Adegboyega PA, Zhang H, Xie J. Ma X, et al. Int J Cancer. 2006 Jan 1;118(1):139-48. doi: 10.1002/ijc.21295. Int J Cancer. 2006. PMID: 16003737 - Sonic hedgehog-Gli1 pathway in colorectal adenocarcinomas.
Bian YH, Huang SH, Yang L, Ma XL, Xie JW, Zhang HW. Bian YH, et al. World J Gastroenterol. 2007 Mar 21;13(11):1659-65. doi: 10.3748/wjg.v13.i11.1659. World J Gastroenterol. 2007. PMID: 17461467 Free PMC article. - Sonic hedgehog and Gli1 expression predict outcome in resected pancreatic adenocarcinoma.
Maréchal R, Bachet JB, Calomme A, Demetter P, Delpero JR, Svrcek M, Cros J, Bardier-Dupas A, Puleo F, Monges G, Hammel P, Louvet C, Paye F, Bachelier P, Le Treut YP, Vaillant JC, Sauvanet A, André T, Salmon I, Devière J, Emile JF, Van Laethem JL. Maréchal R, et al. Clin Cancer Res. 2015 Mar 1;21(5):1215-24. doi: 10.1158/1078-0432.CCR-14-0667. Epub 2014 Dec 31. Clin Cancer Res. 2015. PMID: 25552484 - Hedgehog signaling pathway and gastric cancer.
Katoh Y, Katoh M. Katoh Y, et al. Cancer Biol Ther. 2005 Oct;4(10):1050-4. doi: 10.4161/cbt.4.10.2184. Epub 2005 Oct 18. Cancer Biol Ther. 2005. PMID: 16258256 Review. - Therapeutic targeting of the Hedgehog-GLI pathway in prostate cancer.
Sanchez P, Clement V, Ruiz i Altaba A. Sanchez P, et al. Cancer Res. 2005 Apr 15;65(8):2990-2. doi: 10.1158/0008-5472.CAN-05-0439. Cancer Res. 2005. PMID: 15833820 Review.
Cited by
- "GLI1 Subcellular Localization and Overexpression as Prognostic Factors for Disease-Free Survival in Colorectal Carcinoma".
Rather TB, Parveiz I, Rashid G, Akhtar K, Mudassar S, Wani RA, Besina S, Haq RIU. Rather TB, et al. J Gastrointest Cancer. 2024 Sep;55(3):1359-1379. doi: 10.1007/s12029-024-01090-y. Epub 2024 Jul 17. J Gastrointest Cancer. 2024. PMID: 39018008 - Gastric adenocarcinoma of the fundic gland type: A review of the literature.
Zhai Z, Hu W, Huang Z, Chen Z, Lu S, Gong W. Zhai Z, et al. JGH Open. 2023 Nov 30;7(12):812-825. doi: 10.1002/jgh3.13014. eCollection 2023 Dec. JGH Open. 2023. PMID: 38162862 Free PMC article. Review. - Integrative Analysis of Bulk RNA-Seq and Single-Cell RNA-Seq Unveils the Characteristics of the Immune Microenvironment and Prognosis Signature in Prostate Cancer.
Wang R, Xiao Y, Pan M, Chen Z, Yang P. Wang R, et al. J Oncol. 2022 Jul 19;2022:6768139. doi: 10.1155/2022/6768139. eCollection 2022. J Oncol. 2022. PMID: 35909899 Free PMC article. - Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances.
Ma C, Hu K, Ullah I, Zheng QK, Zhang N, Sun ZG. Ma C, et al. Front Oncol. 2022 Apr 1;12:729088. doi: 10.3389/fonc.2022.729088. eCollection 2022. Front Oncol. 2022. PMID: 35433472 Free PMC article. Review. - Dual activation of Hedgehog and Wnt/β-catenin signaling pathway caused by downregulation of SUFU targeted by miRNA-150 in human gastric cancer.
Peng Y, Zhang X, Lin H, Deng S, Qin Y, He J, Hu F, Zhu X, Feng X, Wang J, Wei Y, Fan X, Lin H, Ashktorab H, Smoot D, Lv Y, Li S, Meltzer SJ, Jin Z. Peng Y, et al. Aging (Albany NY). 2021 Apr 12;13(7):10749-10769. doi: 10.18632/aging.202895. Epub 2021 Apr 12. Aging (Albany NY). 2021. PMID: 33848981 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical