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Ubiquitin B in Cervical Cancer: Critical for the Maintenance of Cancer Stem-Like Cell Characters
- Source :
- PLoS ONE, PLoS ONE, Vol 8, Iss 12, p e84457 (2013)
- Publication Year :
- 2013
-
Abstract
- Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate. Ubiquitin, which is a small, highly conserved protein expressed in all eukaryotic cells, can be covalently linked to certain target proteins to mark them for degradation by the ubiquitin-proteasome system. Previous studies highlight the essential role of Ubiquitin B (UbB) and UbB-dependent proteasomal protein degradation in histone deacetylase inhibitor (HDACi) -induced tumor selectivity. We hypothesized that UbB plays a critical role in the function of cervical cancer stem cells. We measured endogenous UbB levels in mammospheres in vitro by real-time PCR and Western blotting. The function of UbB in cancer stem-like cells was assessed after knockdown of UbB expression in prolonged Trichostatin A-selected HeLa cells (HeLa/TSA) by measuring in vitro cell proliferation, cell apoptosis, invasion, and chemotherapy resistance as well as by measuring in vivo growth in an orthotopic model of cervical cancer. We also assessed the cancer stem cell frequency, tumorsphere formation, and in vivo growth of human cervical cancer xenografts after UbB silencing. We found that HeLa/TSA were resistant to chemotherapy, highly expressed the UbB gene and the stem cell markers Sox2, Oct4 and Nanog. These cells also displayed induced differentiation abilities, including enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Furthermore, an elevated expression of UbB was shown in the tumor samples of chemotherapy patients. Silencing of UbB inhibited tumorsphere formation, lowered the expression of stem cell markers and decreased cervical xenograft growth. Our results demonstrate that UbB was significantly increased in prolonged Trichostatin A-selected HeLa cells and it played a key role in the maintenance of cervical cancer stem-like cells.
- Subjects :
- Homeobox protein NANOG
Pathology
medicine.medical_specialty
lcsh:Medicine
Uterine Cervical Neoplasms
Stem cell marker
Hydroxamic Acids
HeLa
Mice
Ubiquitin
SOX2
Cancer stem cell
Spheroids, Cellular
medicine
Animals
Humans
Gene Silencing
RNA, Small Interfering
lcsh:Science
Multidisciplinary
biology
Ubiquitin B
lcsh:R
Correction
biology.organism_classification
Up-Regulation
Gene Expression Regulation, Neoplastic
Histone Deacetylase Inhibitors
Cell Transformation, Neoplastic
Drug Resistance, Neoplasm
biology.protein
Cancer research
Neoplastic Stem Cells
lcsh:Q
Female
Stem cell
Research Article
HeLa Cells
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....c2e31cff8390fc8c7136581cda267d85