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Inhibitory effect of Nodal on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma of uterus
- Source :
- Biochemical and biophysical research communications. 440(4)
- Publication Year :
- 2013
-
Abstract
- Cancers consist of heterogeneous populations. Recently, it has been demonstrated that cells with tumorigenic potential are limited to a small population, called cancer-initiating cells (CICs). Aldehyde dehydrogenase 1 (ALDH1) is one of the markers of CICs. We previously reported that ALDH1-high cases of uterine endometrioid adenocarcinoma showed poor prognosis, and ALDH1-high population of endometrioid adenocarcinoma cell line was more tumorigenic, resistant to anti-cancer drugs, and invasive than ALDH1-low population. Here, the regulatory signaling for ALDH1 was examined. The inhibition of TGF-β signaling increased ALDH1-high population. Among TGF-β family members, Nodal expression and ALDH1 expression levels were mutually exclusive. Immunohistochemical analysis on clinical samples revealed Nodal-high tumor cells to be ALDH-low and vise versa, suggesting that Nodal may inhibit ALDH1 expression via stimulating TGF-β signaling in uterine endometrioid adenocarcinoma. In fact, the addition of Nodal to endometrioid adenocarcinoma cell line reduced ALDH1-high population. Although ALDH1 mRNA level was not affected, the amount of ALDH1 protein appeared to be reduce by Nodal through ubiquitine-proteasome pathway. The regulation of TGF-β signaling might be a novel therapeutic target of CICs in endometrioid adenocarcinoma.
- Subjects :
- medicine.medical_specialty
Nodal Protein
Population
Biophysics
Uterus
Aldehyde dehydrogenase
Biology
Biochemistry
Aldehyde Dehydrogenase 1 Family
Transforming Growth Factor beta
Internal medicine
Cell Line, Tumor
medicine
Endometrioid adenocarcinoma
Humans
education
Molecular Biology
education.field_of_study
Ubiquitination
Retinal Dehydrogenase
Cell Biology
Endometrial Neoplasms
Isoenzymes
medicine.anatomical_structure
Endocrinology
Cell culture
Proteolysis
Cancer research
biology.protein
Immunohistochemistry
Female
NODAL
Carcinoma, Endometrioid
Transforming growth factor
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 440
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....e40da03a04e4857418ebee78e0328ff6