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Nuclear FAM289-Galectin-1 interaction controls FAM289-mediated tumor promotion in malignant glioma
- Source :
- Journal of Experimental & Clinical Cancer Research, Vol 38, Iss 1, Pp 1-19 (2019), Journal of Experimental & Clinical Cancer Research : CR
- Publication Year :
- 2019
- Publisher :
- BMC, 2019.
-
Abstract
- Background FAM92A1–289(abbreviated FAM289) is recognized as one of the newly-discovered putative oncogenes. However, its role and molecular mechanisms in promoting cancer progression has not yet been elucidated. This study was performed to reveal its oncogenic functions and molecular mechanisms in human glioblastoma multiforme (GBM) cell models with knockdown or overexpression of FAM289 in vitro and in vivo. Methods To elucidate the molecular mechanisms underlying FAM289-mediated tumor progression, the protein-protein interaction between FAM289 and Galectin-1 was verified by co-immunoprecipitation, followed by an analysis of the expression and activity of Galectin-1-associated signaling molecules. Knockdown and overexpression of FAM289 in glioma cells were applied for investigating the effects of FAM289 on cell growth, migration and invasion. The determination of FAM289 expression was performed in specimens from various stages of human gliomas. Results FAM289-galectin-1 interaction and concomitant activation of the extracellular signal-regulated kinase (ERK) pathway participated in FAM289-mediated tumor-promoting function. Since the expression of DNA methyl transferase 1 (DNMT1) and DNA methyl transferase 3B (DNMT3B) was regulated by FAM289 in U251 and U87-MG glioma cells, Galectin-1 interaction with FAM289 may promote FAM289 protein into the cell nucleus and activate the ERK pathway, thereby upregulating DNMTs expression. Drug resistance tests indicated that FAM289-mediated TMZ resistance was through stem-like property acquisition by activating the ERK pathway. The correlation between FAM289, Galectin-1 expression and the clinical stage of gliomas was also verified in tissue samples from glioblastoma patients. Conclusions Our results suggest that high expression of FAM289 in GBM tissues correlated with poor prognosis. FAM289 contributes to tumor progression in malignant glioma by interacting with Galectin-1 thereby promoting FAM289 protein translocation into the cell nucleus. FAM289 in the nucleus activated the ERK pathway, up regulated DNMTs expression and induced stem-like property gene expression which affects drug resistance of glioma cells to TMZ. This study provided functional evidence for FAM289 to be developed as a therapeutic target for cancer treatment. Electronic supplementary material The online version of this article (10.1186/s13046-019-1393-7) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Cancer Research
Cell signaling
Galectin 1
Cell
FAM289
lcsh:RC254-282
03 medical and health sciences
Mice
0302 clinical medicine
Cell Movement
Glioma
Cell Line, Tumor
medicine
Animals
Humans
Neoplasm Metastasis
Cell Proliferation
Neoplasm Staging
Gene knockdown
Chemistry
Cell growth
Research
NF-kappa B
Proteins
DNMTs
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Oncology
Tumor progression
030220 oncology & carcinogenesis
Gene Knockdown Techniques
Cancer research
Disease Progression
Tumor promotion
ERK pathway
Glioblastoma multiforme cell
Protein Binding
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 17569966
- Volume :
- 38
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental & Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....cf2574fb4098805aa514e2123c76661d