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Carboxy terminus of HSP70 ‐interacting protein ( CHIP ) attenuates the stemness of thyroid cancer cells through decreasing OCT4 protein stability
Author(s) -
Xu Ying,
Xu Gang,
Dang Huimin,
Qu Wei,
Chang Dan,
He Xin,
Li Minmin,
Wang Qian
Publication year - 2021
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.23072
Subject(s) - cancer cell , cancer stem cell , chemistry , thyroid cancer , transcription factor , gene knockdown , cancer research , microbiology and biotechnology , biology , stem cell , cancer , apoptosis , biochemistry , gene , genetics
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.