2. Academic Validation
  3. Obesity-Associated TRIM15 Promotes the Proliferation of Esophageal Adenocarcinoma Through the YY2/FOXRED1 Axis

Obesity-Associated TRIM15 Promotes the Proliferation of Esophageal Adenocarcinoma Through the YY2/FOXRED1 Axis

  • Adv Sci (Weinh). 2025 Nov 14:e17330. doi: 10.1002/advs.202417330.
Haohui Wang 1 2,  Chong Yang 3,  Dayuan Luo 1 2,  Pingting Liu 4,  Zhen Zeng 5 6,  Weilin Peng 1 2,  Dongzi Peng 7 8,  Hao Su 9 10 11,  Xiaoxiong Xiao 12 13,  Haiqin Wang 5 6,  Xin Jin 9 10 11
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • 2 Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • 3 Department of Hepatobiliary and Pancreatic Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
  • 4 Department of Health Management Center, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, 410008, China.
  • 5 Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • 6 Hunan Clinical Medical Research Center for Geriatric Syndrome, Changsha, Hunan, 410011, China.
  • 7 Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • 8 Research Center of Digestive Disease, Central South University, Changsha, Hunan, 410011, China.
  • 9 Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
  • 10 Uro-Oncology Institute of Central South University, Changsha, Hunan, 410011, China.
  • 11 Furong Laboratory, Central South University, Changsha, Hunan, 410000, China.
  • 12 Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
  • 13 Xiangya Lung Cancer Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
PMID: 41237333 DOI: 10.1002/advs.202417330
Abstract

Obesity has been identified as an independent risk factor for gastroesophageal reflux disease (GERD) and esophageal adenocarcinoma (EAC). Oxidative stress and inflammation driven by chronic GERD are the main causes of the tumorigenesis of EAC, but the underlying mechanism remains elusive. Here, the inflammation-upregulated E3 Ligase, tripartite motif 15 (TRIM15), is identified as a key driver of obesity-associated EAC. TRIM15 promotes the degradation of YY2 is demonstrated through the ubiquitin-proteasome system, which in turn dysregulates lipid metabolism and enhances the proliferation of EAC cells. Furthermore, YY2 transcriptionally is shown that increases FOXRED1 expression. FOXRED1 is subsequently identified as an essential effector for the TRIM15-induced dysregulation of lipid and energy metabolism in EAC cells. Thus, a novel obesity-associated TRIM15/YY2/FOXRED1 axis is identified that contributes to the proliferation of EAC. Given that lipid metabolism regulates Ferroptosis by controlling cellular processes associated with phospholipid peroxidation. The TRIM15/YY2/FOXRED1 axis demonstrates that it modulates SLC3A2 expression via the mTOR/c-Myc pathway, thereby regulating GPX4 levels to influence EAC sensitivity to ferroptosis-inducing compounds and proposing a therapeutic strategy for EAC.

Keywords

TRIM15; esophageal adenocarcinoma; ferroptosis; lipid metabolism; obesity.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z