KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11-Reference-Cited by-同舟云学术

KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11

Published:2023-01-01 Issue:1 Volume:18 Page:
ISSN:2391-5463
Container-title:Open Medicine
language:en
Short-container-title:

Author:

Deng Chongwen¹,Ye Chunhua²,Liao Xiwang²,Zhou Fuyin²,Shi Youxiong²,Zhong Hong²,Huang Junbiao²

Affiliation:

1. Department of General Surgery, Loudi Central Hospital , No. 51, Changqing Middle Street , Loudi , 417000 , People’s Republic of China

2. Department of General Surgery, Loudi Central Hospital , Loudi , 417000 , People’s Republic of China

Abstract

Abstract The molecular mechanisms of epigenetic regulation in gastric cancer development are not yet well established. In this study, we demonstrated that KMT2A was highly expressed in gastric cancer and associated with poor outcomes of patients and revealed that KMT2A was significantly associated with stemness and increased nuclear β-catenin in gastric cancer. Mechanistically, KMT2A activated the translocation of β-catenin into the nucleus of gastric cancer cells, and then, β-catenin served as a coactivator of KLF11, which promoted the expression of specific gastric cancer stemness-related molecules, including SOX2 and FOXM1. Together, KMT2A is an important epigenetic regulator of gastric cancer stemness, which provides a novel insight to the potential application of targeting against KMT2A in treating gastric cancer.

Publisher

Walter de Gruyter GmbH

Subject

General Medicine

Link

https://www.degruyter.com/document/doi/10.1515/med-2023-0764/pdf

Reference40 articles.

1. Ebrahimi V, Soleimanian A, Ebrahimi T, Azargun R, Yazdani P, Eyvazi S, et al. Epigenetic modifications in gastric cancer: Focus on DNA methylation. Gene. 2020;742:144577.

2. Fattahi S, Amjadi-Moheb F, Tabaripour R, Ashrafi GH, Akhavan-Niaki H. PI3K/AKT/mTOR signaling in gastric cancer: Epigenetics and beyond. Life Sci. 2020;262:118513.

3. Cui H, Hu Y, Guo D, Zhang A, Gu Y, Zhang S, et al. DNA methyltransferase 3A isoform b contributes to repressing E-cadherin through cooperation of DNA methylation and H3K27/H3K9 methylation in EMT-related metastasis of gastric cancer. Oncogene. 2018;37(32):4358–71.

4. Singh A, Chang TY, Kaur N, Hsu KC, Yen Y, Lin TE, et al. CAP rigidification of MS-275 and chidamide leads to enhanced antiproliferative effects mediated through HDAC1, 2 and tubulin polymerization inhibition. Eur J Med Chem. 2021;215:113169.

5. Yao Y, Liu Z, Huang S, Huang C, Cao Y, Li L, et al. The E3 ubiquitin ligase, FBXW5, promotes the migration and invasion of gastric cancer through the dysregulation of the Hippo pathway. Cell Death Discov. 2022;8(1):79.