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Nipped-B-like Protein Sensitizes Esophageal Squamous Cell Carcinoma Cells to Cisplatin via Upregulation of PUMA
- Source :
- Technology in Cancer Research & Treatment, Technology in Cancer Research & Treatment, Vol 19 (2020)
- Publication Year :
- 2020
- Publisher :
- SAGE Publications, 2020.
-
Abstract
- Nipped-B-like protein plays a pivotal role as a cohesin loading factor in the segregation of chromosomes when cells divide. Accumulating evidence indicates that alterations of this protein are involved in human carcinogenesis, especially in the regulation of chemotherapeutic drug response. However, the role of Nipped-B-like protein in esophageal squamous cell carcinoma remains unknown. In this study, we investigated the relevance of Nipped-B-like protein in the regulation of cisplatin sensitivity in esophageal squamous cell carcinoma. Ectopic expression of Nipped-B-like protein inhibited the growth of COLO-680N cells with low endogenous expression levels of Nipped-B-like protein, and increased sensitivity to cisplatin, a commonly used chemotherapy drug for patients with esophageal squamous cell carcinoma. In contrast, loss of Nipped-B-like protein stimulated the growth of EC9706 and Eca-109 cells with high levels of the protein, and resulted in resistance to cisplatin. P53-upregulated modulator of apoptosis, which is essential in the modulation of cisplatin sensitivity in a variety of cancers, acts as a downstream effector of Nipped-B-like protein. Restoration of this pro-apoptotic protein in Nipped-B-like protein-overexpressing esophageal squamous cell carcinoma cells effectively increased cisplatin sensitivity. Conversely, the silencing of P53-upregulated modulator of apoptosis in Nipped-B-like protein-depleted esophageal squamous cell carcinoma rendered cells resistant to cisplatin. Moreover, Nipped-B-like protein could bind directly to the promoter region of P53-upregulated modulator of apoptosis. In summary, our study addresses the involvement of Nipped-B-like protein in the development of esophageal squamous cell carcinoma, and the modulation of cisplatin sensitivity via regulation of P53-upregulated modulator of apoptosis.
- Subjects :
- Cancer Research
cisplatin
Apoptosis
Cell Cycle Proteins
medicine.disease_cause
lcsh:RC254-282
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Cell Line, Tumor
Proto-Oncogene Proteins
medicine
Humans
cancer
Gene silencing
p53 upregulated modulator of apoptosis
Nipped-B-like protein
Cell Proliferation
030304 developmental biology
Cohesin loading
Cisplatin
0303 health sciences
drug resistance
biology
Chemistry
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Gene Expression Regulation, Neoplastic
p53-upregulated modulator of apoptosis
Oncology
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
biology.protein
Cancer research
Original Article
Ectopic expression
Esophageal Squamous Cell Carcinoma
Apoptosis Regulatory Proteins
Carcinogenesis
medicine.drug
Subjects
Details
- ISSN :
- 15330338 and 15330346
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Technology in Cancer Research & Treatment
- Accession number :
- edsair.doi.dedup.....64a4e3cd59ac1d6f8575032bc1847c60