HIP1R acts as a tumor suppressor in gastric cancer by promoting cancer cell apoptosis and inhibiting migration and invasion through modulating Akt
Open Access
- 16 June 2020
- journal article
- research article
- Published by Wiley in Journal of Clinical Laboratory Analysis
- Vol. 34 (9), e23425
- https://doi.org/10.1002/jcla.23425
Abstract
Background Huntingtin‐interacting protein 1‐related (HIP1R) is a multi‐domain gene that exerts many cellular functions including altering T cell–mediated cytotoxicity and controlling intracellular trafficking. However, its clinical significance and function in gastric cancer (GC) have not been described. Methods The expression levels of HIP1R were tested by the transcriptional and translational expression analysis and immunohistochemistry (IHC) in matched adjacent non‐tumorous vs tumor tissue specimens. The biological function of HIP1R on apoptosis, migration, and proliferation was evaluated by flow cytometry, Transwell, Cell Counting Kit‐8 (CCK‐8) assays, colony formation assays, and EdU labeling assays, respectively. Results We found downregulated HIP1R in GC compared with adjacent non‐tumorous tissue, and HIP1R expression associated with N classification. We further found that the expression of HIP1R could induce apoptosis and inhibit proliferation, migration, invasion of GC cells, possibly through modulating Akt. Conclusions Our data indicate that HIP1R may act as a potential diagnostic biomarker and a tumor suppressor gene in GC, potentially representing a novel therapeutic target for future GC treatment.Keywords
Funding Information
- China Postdoctoral Science Foundation (2018M640267, 2018M640268)
- National Natural Science Foundation of China (81872031, U1908207)
This publication has 48 references indexed in Scilit:
- Clinicopathological significance of claudin-4 in gastric carcinomaWorld Journal of Surgical Oncology, 2013
- IFNγ contributes to the development of gastric epithelial cell metaplasia in Huntingtin interacting protein 1 related (Hip1r)-deficient miceLaboratory Investigation, 2012
- clusterProfiler: an R Package for Comparing Biological Themes Among Gene ClustersOMICS: A Journal of Integrative Biology, 2012
- The origin of pre-neoplastic metaplasia in the stomach: Chief cells emerge from the MistExperimental Cell Research, 2011
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Cytodifferentiation of the postnatal mouse stomach in normal and Huntingtin-interacting protein 1-related-deficient miceAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2010
- Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in miceJCI Insight, 2008
- Clathrin light chains function in mannose phosphate receptor trafficking via regulation of actin assemblyProceedings of the National Academy of Sciences of the United States of America, 2008
- HIP1 and HIP1r Stabilize Receptor Tyrosine Kinases and Bind 3-Phosphoinositides via Epsin N-terminal Homology DomainsJournal of Biological Chemistry, 2004
- Tissue microarrays for high-throughput molecular profiling of tumor specimensNature Medicine, 1998