Correction to: CDK4/6 inhibitors downregulate the ubiquitin-conjugating enzymes UBE2C/S/T involved in the ubiquitin–proteasome pathway in ER + breast cancer (Clinical and Translational Oncology, (2022), 24, 11, (2120-2135), 10.1007/s12094-022-02881-0)

Chih Yi Lin, Chung Jen Yu, Chun Yu Liu, Ta Chung Chao, Chi Cheng Huang, Ling Ming Tseng, Jiun I. Lai*

*Corresponding author for this work

Research output: Contribution to journalComment/debate


The abstract was unstructured in this article and should have read as structured as follows: Abstract Purpose Despite significant improvement in therapeutic development in the past decades, breast cancer remains a formidable cause of death for women worldwide. The hormone positive subtype (HR(+)) (also known as luminal type) is the most prevalant category of breast cancer, comprising ~ 70% of patients. The clinical success of the three CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib has revolutionized the treatment of choice for metastatic HR(+) breast cancer. Accumulating evidence demonstrate that the properties of CDK4/6 inhibitors extend beyond inhibition of the cell cycle, including modulation of immune function, sensitizing PI3K inhibitors, metabolism reprogramming, kinome rewiring, modulation of the proteosome, and many others. The ubiquitin–proteasome pathway (UPP) is a crucial cellular proteolytic system that maintains the homeostasis and turnover of proteins. Methods We performed transcriptional profiling of the HR(+) breast cancer cell lines MCF7 and T47D treated with Palbociclib. Differential expressed genes were analyzed for novel pathways enriched. The results were further validated with biochemical assays and with real world clinical database cohorts. Results We uncovered a novel mechanism that demonstrate the CDK4/6 inhibitors suppress the expression of three ubiquitin conjugating enzymes UBE2C, UBE2S, UBE2T. Further validation in the HR(+) cell lines show that Palbociclib and ribociclib decrease UBE2C at both the mRNA and protein level, but this phenomenon was not shared with abemaciclib. These three E2 enzymes modulate several E3 ubiquitin ligases, including the APC/C complex which plays a role in G1/S progression. We further demonstrate the UBE2C/UBE2T expression levels are associated with breast cancer survival, and HR(+) breast cancer cells demonstrate dependence on the UBE2C. Conclusions Our study suggests a novel link between CDK4/6 inhibitor and UPP pathway, adding to the potential mechanisms of their clinical efficacy in cancer. The formatting of the "Results" section was incorrect, and it should have read as follows: genes discovered to have a fold change of = twofold (1 increased, 189 decreased) (Supplementary Table 1). When we analyzed the DEGs by DAVID, we discovered that the enriched pathways included ribosome related genes, Ubl conjugation pathway, and actin cytoskeleton related genes (Fig. 4b). This suggested that UBE2C knockdown may affect ubiquitin related genes, ribosomal function and translation, and actin related genes. Although this GEO database is a study on prostate cancer, which could reveal prostate cancer specific gene expression profiles, the results could still be valuable for a preliminary understanding of the transcriptome resultant to UBE2C knockdown. The impact of these affected genes on CDK4/6 inhibitor efficacy and on breast cancer remains to be further investigated. The original article has been corrected.

Original languageEnglish
Pages (from-to)2251-2253
Number of pages3
JournalClinical and Translational Oncology
Issue number11
StatePublished - Nov 2022


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