Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Mar 14;23(10):1758-1763.
doi: 10.3748/wjg.v23.i10.1758.

Ghrelin and gastrointestinal stromal tumors

Chang-Zhen Zhu  1 , Dong Liu  1 , Wei-Ming Kang  1 , Jian-Chun Yu  1 , Zhi-Qiang Ma  1 , Xin Ye  1 , Kang Li  1
Affiliations
Review

Ghrelin and gastrointestinal stromal tumors

Chang-Zhen Zhu et al. World J Gastroenterol. .

Abstract

Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors (GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and mRNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/mTOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/mTOR pathway and the development of GISTs.

Keywords: Development; Gastrointestinal stromal tumor; Ghrelin; Occurrence; PI3K/AKT/mTOR pathway.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.

Figures

Figure 1
Figure 1
PI3K/AKT/mTOR pathway and inhibitors in clinical development[29]. Solid lines represent activating actions, and dotted lines represent inhibitory actions. 4EBP1: 4E-binding protein 1; PKB: Protein kinase B; ERK: Extracellular signal-related kinase; IRS1: Insulin receptor substrate 1; MEK: Mitogen-activated protein/ERK kinase; mTOR: Mammalian target of rapamycin; mTORC: mTOR complex; PDK1: Pyruvate dehydrogenase lipoamide kinase isozyme 1; PI3K: Phosphatidylinositol 3-kinase; PIP2: Phosphatidylinositol 4,5-bisphosphate; PIP3: Phosphatidylinositol 3,4,5-trisphosphate; PTEN: Phosphatase and tensin homolog; Rheb: Ras homolog enriched in brain; rpS6: Ribosomal protein S6; RTK: Receptor tyrosine kinase; S6K: Ribosomal S6 kinase; TSC1/2: Tuberous sclerosis protein.
Figure 2
Figure 2
Specific mechanism of ghrelin involved in the protection of pulmonary artery endothelial cells and activation of the PI3K/AKT/mTOR pathway in human pulmonary artery endothelial cells[44-47]. Solid lines represent activating actions, and dotted lines represent inhibitory actions. PIP2: Phosphatidylinositol 4,5-bisphosphate; PIP3: Phosphatidylinositol 3,4,5-trisphosphate.
See this image and copyright information in PMC

References

    1. Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O’Leary TJ, Remotti H, Rubin BP, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol. 2002;33:459–465. - PubMed
    1. Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K; American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373:1097–1104. - PMC - PubMed
    1. Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–580. - PubMed
    1. Hirota S, Ohashi A, Nishida T, Isozaki K, Kinoshita K, Shinomura Y, Kitamura Y. Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology. 2003;125:660–667. - PubMed
    1. Gramza AW, Corless CL, Heinrich MC. Resistance to Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors. Clin Cancer Res. 2009;15:7510–7518. - PubMed

MeSH terms