Carboxy terminus of HSP70‐interacting protein (CHIP) attenuates the stemness of thyroid cancer cells through decreasing OCT4 protein stability

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.

The ubiquitin ligase STUB1 suppresses tumorigenesis of renal cell carcinomas through regulating YTHDF1 stability

“…Previous studies have demonstrated that the E3 ubiquitin ligase STUB1 exhibits a tumor suppressor effect by promoting ubiquitination and degradation of multiple oncogenes in various cancers, including lung cancer [16,17] , breast cancer [7] , prostate cancer [8][9][10] , gastric cancer [21] , colorectal cancer [14] , and thyroid cancer [32] . For example, STUB1 functions as a tumor suppressor in ovarian carcinoma by promoting ubiquitination and degradation of PKM2 [19] .…”

E3 Ubiquitin Ligase CHIP Inhibits the Interaction between Hsp90β and MAST1 to Repress Radiation Resistance in Non-Small-Cell Lung Cancer Stem Cells

“…Besides, CHIP is reported to repress tumor metastasis in lung cancer by polyubiquitination of ovarian tumor domain-containing protein 3 to promote its degradation [ 28 ]. Interestingly, it was revealed that CHIP could alleviate the stemness of thyroid cancer cells through downregulation of Oct4 protein stability [ 29 ]. Additionally, CHIP mediates CD166 protein stability via the ubiquitin proteasome system, thereby repressing the properties of CSCs in head and neck cancer [ 21 ].…”