1. Academic Validation
  2. Nanog mediated by FAO/ACLY signaling induces cellular dormancy in colorectal cancer cells

Nanog mediated by FAO/ACLY signaling induces cellular dormancy in colorectal cancer cells

  • Cell Death Dis. 2022 Feb 17;13(2):159. doi: 10.1038/s41419-022-04606-1.
Meng Zhang  # 1 2 Ruyi Peng  # 1 2 Haizhou Wang  # 1 2 Zhenwei Yang 1 2 Hailin Zhang 1 2 Yangyang Zhang 1 2 Meng Wang 1 2 Hongling Wang 1 2 Jun Lin 1 2 Qiu Zhao 3 4 Jing Liu 5 6
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
  • 2 Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan, 430071, China.
  • 3 Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. qiuzhao@whu.edu.cn.
  • 4 Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan, 430071, China. qiuzhao@whu.edu.cn.
  • 5 Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. liujing_GI@whu.edu.cn.
  • 6 Hubei Clinical Center & Key Lab of Intestinal & Colorectal Diseases, Wuhan, 430071, China. liujing_GI@whu.edu.cn.
  • # Contributed equally.
Abstract

Dormant Cancer cells drive recurrence and drug resistance, which lead to poor prognosis in colorectal Cancer (CRC). The mechanisms that regulate the entry of Cancer cells into dormancy remain to be extensively studied. Nanog is a master transcription factor to maintain the self-renewal and pluripotency of stem cells. Since dormant Cancer cells are similar to quiescent Cancer Stem Cells, the correlation between dormant state and Nanog in CRC is worth to be explored. Serum deprivation is a common method to establish experimental cellular dormancy model. Here, we verified that serum deprivation-induced CRC cells to enter a cellular dormancy state, characterized by no proliferation, no death, no senescence, resistance to chemotherapy, high expression of dormant markers, metabolic suppression, and recovery to active status. Interestingly, we further identified that Nanog was upregulated in dormant CRC cells. Nanog knockdown could destroy the dormant state of serum-deprived CRC cells while Nanog overexpression could induce dormancy in CRC cells. Mechanistically, Nanog was regulated through a fatty acid oxidation (FAO)/ATP Citrate Lyase (ACLY)-dependent pathway. FAO increased ACLY expression to promote the synthesis of acetyl-CoA, which was transferred by P300 to accelerate H3K27 acetylation of Nanog promoter. Then, Nanog upregulation increased the transcription of P21 and P27, which promoted the dormancy of CRC cells. Our findings revealed that Nanog could induce cellular dormancy in CRC cells and unlocked a specific mechanism to govern the process.

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