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Carboxy terminus of HSP70-interacting protein (CHIP) attenuates the stemness of thyroid cancer cells through decreasing OCT4 protein stability
- Source :
- Environmental toxicologyREFERENCES. 36(4)
- Publication Year :
- 2020
-
Abstract
- Cancer cell stemness results in the occurrence and progression of tumors and Oct4 (octamer-binding transcription factor) has been confirmed to be a critical contributor and marker of cancer cell stemness. Here, we aimed to explore the underlying mechanisms contributing to Oct4 protein stability, which is necessary for thyroid cancer (TC) cell stemness. We indicated that carboxy terminus of HSP70-interacting protein (CHIP) protein was lowly expressed in TC tissues and cells, and positively correlated with the overall survival of TC patients. By analyzing the co-expression network in TC tissues, we found that CHIP and Oct4 expression exhibited a negative correlation. Functional experiments showed that CHIP knockdown promoted the stemness of TC cells, while CHIP overexpression reduced the stemness of TC spheroids formed by TC cells, in which CHIP expression was significantly decreased. Furthermore, CHIP had no effect on TC cell viability. Mechanistic studies revealed that CHIP directly interacted with Oct4 protein and induced Oct4 ubiquitination, whereas a catalytic CHIP mutant (H260Q) did not. And CHIP regulated the stemness of TC cells in an Oct4-dependent manner. Overall, this work indicates that the CHIP/Oct4 axis is essential for TC cell stemness.
- Subjects :
- Male
Cell Survival
Health, Toxicology and Mutagenesis
Ubiquitin-Protein Ligases
Mutant
Cell
010501 environmental sciences
Management, Monitoring, Policy and Law
Toxicology
01 natural sciences
03 medical and health sciences
0302 clinical medicine
Ubiquitin
Cell Line, Tumor
medicine
Cytotoxic T cell
Humans
Viability assay
Thyroid Neoplasms
Transcription factor
0105 earth and related environmental sciences
Cell Proliferation
Gene knockdown
biology
Chemistry
Protein Stability
Ubiquitination
General Medicine
Cell biology
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
030220 oncology & carcinogenesis
Gene Knockdown Techniques
embryonic structures
Cancer cell
biology.protein
Neoplastic Stem Cells
Octamer Transcription Factor-3
Subjects
Details
- ISSN :
- 15227278
- Volume :
- 36
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Environmental toxicologyREFERENCES
- Accession number :
- edsair.doi.dedup.....bdfa1c01fad6f5638782a40f0080047b