The biological impacts of CEBPD on urothelial carcinoma development and progression

Ti-Chun Chan; Yow-Ling Shiue; Chien-Feng Li

doi:10.3389/fonc.2023.1123776

The biological impacts of CEBPD on urothelial carcinoma development and progression

Front Oncol. 2023 Jan 27:13:1123776. doi: 10.3389/fonc.2023.1123776. eCollection 2023.

Authors

Ti-Chun Chan^{1

2}, Yow-Ling Shiue³, Chien-Feng Li^{1

2

4}

Affiliations

¹ Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
² National Health Research Institutes, National Institute of Cancer Research, Tainan, Taiwan.
³ Institute of Precision Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan.
⁴ Department of Clinical Medicine, Chi Mei Medical Center, Tainan, Taiwan.

Abstract

Urothelial carcinoma (UC), which includes urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC), is one of the most common malignancies worldwide. Accordingly, a comprehensive understanding of the underlying mechanism governing UC development is compulsory. Aberrant CCAAT/enhancer-binding protein delta (CEBPD), a transcription factor, displays an oncogene or tumor suppressor depending on tumor type and microenvironments. However, CEBPD has been reported to possess a clear oncogenic function in UC through multiple regulation pathways. Genomic amplification of CEBPD triggered by MYC-driven genome instability is frequently examined in UC that drives CEBPD overexpression. Upregulated CEBPD transcriptionally suppresses FBXW7 to stabilize MYC protein and further induces hexokinase II (HK2)-related aerobic glycolysis that fuels cell growth. Apart from the MYC-dependent pathway, CEBPD also downregulates the level of hsa-miR-429 to enhance HK2-associated glycolysis and induce angiogenesis driven by vascular endothelial growth factor A (VEGFA). Additionally, aggressive UC is attributed to the tumor metastasis regulated by CEBPD-induced matrix metalloproteinase-2 (MMP2) overexpression. Furthermore, elevated CEBPD induced by cisplatin (CDDP) is identified to have dual functions, namely, CDDP-induced chemotherapy resistance or drive CDDP-induced antitumorigenesis. Given that the role of CEBPD in UC is getting clear but pending a more systemic reappraisal, this review aimed to comprehensively discuss the underlying mechanism of CEBPD in UC tumorigenesis.

Keywords: CEBPD; chromosomal instabilities; glycolysis; resistance; urothelial carcinoma.

Publication types

Review

Grants and funding

This work was sponsored by Taiwan National Ministry of Science and Technology (111-2628-B-384 -001 to CF Li) and National Health Research Institutes (CA-110-PP-11 to CF Li).