The role of SIRT1 in the development of gastrointestinal tumors

Gastrointestinal tumors, including esophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC) and, pose significant global health challenges due to their high morbidity and mortality rates. SIRT1, an NAD+-dependent deacetylase, plays diverse roles in physiological processes and has been...

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Main Authors: Yueming Zhang, Xiaokai Zhou, Jinghui Zhai, Jie Ma, Sixi Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1606530/full
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author Yueming Zhang
Xiaokai Zhou
Xiaokai Zhou
Jinghui Zhai
Jie Ma
Sixi Zhang
author_facet Yueming Zhang
Xiaokai Zhou
Xiaokai Zhou
Jinghui Zhai
Jie Ma
Sixi Zhang
author_sort Yueming Zhang
collection DOAJ
description Gastrointestinal tumors, including esophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC) and, pose significant global health challenges due to their high morbidity and mortality rates. SIRT1, an NAD+-dependent deacetylase, plays diverse roles in physiological processes and has been implicated in cancer development. This review examines the dual roles of SIRT1 in gastrointestinal tumors. In EC, SIRT1 consistently promotes tumor progression, with high SIRT1 expression associated with advanced TNM stage, poor prognosis, lymph node metastasis, and inferior overall survival. In GC, SIRT1 similarly promotes tumor progression via autophagy and chemoresistance, but studies also highlight its potential anti-cancer effects through ferroptosis regulation. In CRC, SIRT1 is often overexpressed and promotes tumor progression through mechanisms involving p53 inhibition, activation of the Wnt/β-catenin pathway, and regulation of Epithelial-Mesenchymal Transition (EMT). However, conflicting evidence suggests SIRT1 can also act as a tumor suppressor by inhibiting β-catenin and nuclear factor-κB (NF-κB) signaling. The dual nature of SIRT1 underscores the need for context-specific understanding of its function. Future research should focus on elucidating SIRT1’s mechanisms and developing personalized therapeutic strategies targeting SIRT1.
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spelling doaj-art-d1be10ca60aa4bb998bde3d3a823c9802025-08-20T02:35:39ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-06-011310.3389/fcell.2025.16065301606530The role of SIRT1 in the development of gastrointestinal tumorsYueming Zhang0Xiaokai Zhou1Xiaokai Zhou2Jinghui Zhai3Jie Ma4Sixi Zhang5Department of Clinical Pharmacy, The First Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Clinical Pharmacy, The First Hospital of Jilin University, Changchun, Jilin, ChinaClinical Medical College, The First Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Clinical Pharmacy, The First Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Clinical Pharmacy, The First Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Clinical Pharmacy, The First Hospital of Jilin University, Changchun, Jilin, ChinaGastrointestinal tumors, including esophageal cancer (EC), gastric cancer (GC) and colorectal cancer (CRC) and, pose significant global health challenges due to their high morbidity and mortality rates. SIRT1, an NAD+-dependent deacetylase, plays diverse roles in physiological processes and has been implicated in cancer development. This review examines the dual roles of SIRT1 in gastrointestinal tumors. In EC, SIRT1 consistently promotes tumor progression, with high SIRT1 expression associated with advanced TNM stage, poor prognosis, lymph node metastasis, and inferior overall survival. In GC, SIRT1 similarly promotes tumor progression via autophagy and chemoresistance, but studies also highlight its potential anti-cancer effects through ferroptosis regulation. In CRC, SIRT1 is often overexpressed and promotes tumor progression through mechanisms involving p53 inhibition, activation of the Wnt/β-catenin pathway, and regulation of Epithelial-Mesenchymal Transition (EMT). However, conflicting evidence suggests SIRT1 can also act as a tumor suppressor by inhibiting β-catenin and nuclear factor-κB (NF-κB) signaling. The dual nature of SIRT1 underscores the need for context-specific understanding of its function. Future research should focus on elucidating SIRT1’s mechanisms and developing personalized therapeutic strategies targeting SIRT1.https://www.frontiersin.org/articles/10.3389/fcell.2025.1606530/fullSIRT1colorectal cancergastric cancertumor progressionchemoresistance
spellingShingle Yueming Zhang
Xiaokai Zhou
Xiaokai Zhou
Jinghui Zhai
Jie Ma
Sixi Zhang
The role of SIRT1 in the development of gastrointestinal tumors
Frontiers in Cell and Developmental Biology
SIRT1
colorectal cancer
gastric cancer
tumor progression
chemoresistance
title The role of SIRT1 in the development of gastrointestinal tumors
title_full The role of SIRT1 in the development of gastrointestinal tumors
title_fullStr The role of SIRT1 in the development of gastrointestinal tumors
title_full_unstemmed The role of SIRT1 in the development of gastrointestinal tumors
title_short The role of SIRT1 in the development of gastrointestinal tumors
title_sort role of sirt1 in the development of gastrointestinal tumors
topic SIRT1
colorectal cancer
gastric cancer
tumor progression
chemoresistance
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1606530/full
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