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A novel mechanism for C1GALT1 in the regulation of gastric cancer progression
- Source :
- Cell & Bioscience, Cell & Bioscience, Vol 11, Iss 1, Pp 1-15 (2021)
- Publication Year :
- 2021
- Publisher :
- BioMed Central, 2021.
-
Abstract
- Background Gastric cancer (GC) is a highly aggressive and lethal disease around the world. High expression of core 1 β 1, 3-galactosyltransferase 1 (C1GALT1), the primary enzyme responsible for protein O-glycosylation, plays a critical role in gastric carcinogenesis. However, proteins that can be O-glycosylated by C1GALT1 in GC have not been completely elucidated. Also, the mechanism leading to its upregulation in GC is currently unknown. Results Using public databases and our patient samples, we confirmed that C1GALT1 expression was upregulated at both the mRNA and protein levels in GC tissues. Elevated expression of C1GALT1 protein was closely associated with advanced TNM stage, lymph node metastasis, tumor recurrence, and poor overall survival. With gain- and loss-of-function approaches, we demonstrated that C1GALT1 promoted GC cell proliferation, migration, and invasion. By employing lectin pull-down assay and mass spectrometry, integrin α5 was identified as a new downstream target of C1GALT1 in GC. C1GALT1 was able to modify O-linked glycosylation on integrin α5 and thereby modulate the activation of the PI3K/AKT pathway. Functional experiments indicated that integrin α5 inhibition could reverse C1GALT1-mediated tumor growth and metastasis both in vitro and in vivo. Moreover, transcription factor SP1 was found to bind to the C1GALT1 promoter region and activated its expression. Further investigation proved that miR-152 negatively regulated C1GALT1 expression by directly binding to its 3′ -UTR. Conclusions Our findings uncover a novel mechanism for C1GALT1 in the regulation of GC progression. Thus, C1GALT1 may serve as a promising target for the diagnosis and treatment of GC.
- Subjects :
- QH301-705.5
Integrin
QD415-436
Biochemistry
General Biochemistry, Genetics and Molecular Biology
Metastasis
Downregulation and upregulation
medicine
Biology (General)
PI3K/AKT/mTOR pathway
C1GALT1
Sp1 transcription factor
biology
Cell growth
Chemistry
Research
Cancer
Promoter
medicine.disease
Malignant progression
Cancer research
biology.protein
Gastric cancer
TP248.13-248.65
Glycosyltransferase
Biotechnology
Subjects
Details
- Language :
- English
- ISSN :
- 20453701
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cell & Bioscience
- Accession number :
- edsair.doi.dedup.....74049a69e89851cd2279f088d63552d5