Noncanonical Functions of the Polycomb Group Protein EZH2 in Breast Cancer

Abstract

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TPH1 and 5-HT7 Receptor Overexpression Leading to Gemcitabine-Resistance Requires Non-Canonical Permissive Action of EZH2 in Pancreatic Ductal Adenocarcinoma

“…The automethylation of EZH2 is reported as a self-activating mechanism for PRC2 [38]. However, in the current study we found that SUZ12 was not binding with EZH2, indicating the PRC2-independent action of EZH2 in PDAC as reported in breast cancer [49]. Interestingly, although nuclear p-STAT3 was involved in EZH2 transactivating action, p-STAT3 as well as STAT3 were not methylated in PDAC, which is different from other cancer cell types that methylated STAT3 by EZH2 is involved in tumorigenesis of glioblastoma stem-like cells [14].…”

“…Overall, EZH2 permits transactivation of TPH1 and 5-HT 7 , allowing the TPH1-5-HT-5-HT 7 axis to stimulate PI3K/Akt and JAK2/STAT3 pathways in a feed-forward manner in PDAC, leading to maintenance of pancreatic CSC populations and drug resistance. The transactivation of TPH1 and 5-HT independent action of EZH2 in PDAC as reported in breast cancer [49]. Interestingly, although nuclear p-STAT3 was involved in EZH2 transactivating action, p-STAT3 as well as STAT3 were not methylated in PDAC, which is different from other cancer cell types that methylated STAT3 by EZH2 is involved in tumorigenesis of glioblastoma stem-like cells [14].…”

Targeting Triple-Negative Breast Cancer by a Novel Proteolysis Targeting Chimera Degrader of Enhancer of Zeste Homolog 2

“…EZH2 drives oncogenesis not only in a canonical H3K27me3-dependent manner but also through non-canonical H3K27me3-independent functions. , For example, EZH2 has been shown to methylate non-histone proteins such as GATA4, STAT3, and β-catenin, among others. EZH2 can also act as a transcriptional activator by direct binding to a promoter region of several targets, such as NOTCH1 and TRIM28 .…”

EZH2 Protein Expression in Triple-negative Breast Cancer Treated With Neoadjuvant Chemotherapy: An Exploratory Study of Association With Tumor Response and Prognosis

“…[44][45][46] In addition to upregulation of NOTCH1 resulting in stem cell expansion, EZH2 has been shown to directly promote invasion and metastasis by forming a complex with the cytoskeletal protein vinculin. 29,47 Our results suggest that EZH2 may therefore play a central role in chemotherapy-mediated cancer cell dissemination during NAC.…”