2. Academic Validation
  3. Anterior cingulate cortex mediates the comorbidity between colorectal cancer and depression-like behaviors

Anterior cingulate cortex mediates the comorbidity between colorectal cancer and depression-like behaviors

  • Commun Biol. 2025 Aug 27;8(1):1284. doi: 10.1038/s42003-025-08719-z.
Mingchuan Huang # 1,  Shujin He # 2,  Yuting Wang # 2,  Yixiu Zeng 3,  Qiuyi Chen 3,  Yongyu Chen 2,  Xinyu Wang 3,  Yiyi Li 3,  Lin Chen 2,  Shuai Zheng 2,  Yu Wang 2,  Shuang Mo 4,  Anjia Han 5,  Pei Xia 6
Affiliations

Affiliations

  • 1 Department of Pediatric Surgery, the First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China.
  • 2 Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China.
  • 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
  • 4 Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China. mosh7@mail.sysu.edu.cn.
  • 5 Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China. hananjia@mail.sysu.edu.cn.
  • 6 Department of Pathology, the First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China. xiap8@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 40866718 DOI: 10.1038/s42003-025-08719-z
Abstract

Clinical studies demonstrate that comorbidity between colorectal Cancer (CRC) and depression is common, leading to a higher mortality risk among CRC patients. However, the mechanisms remain largely unexplored. The role of core brain regions in comorbidity of CRC and depression and whether modulating these regions can improve both depression-like symptoms and CRC progression have yet to be clarified. In this study, we establish a mouse (Mus musculus) model of CRC and observe that mice with orthotopic colorectal Cancer (CRC mice) display depression-like behaviors. Through c-Fos mapping, network analysis, correlation analysis, and inverse tracing, we identify the anterior cingulate cortex (ACC) as a central node within the depression-related brain network in CRC mice. Notably, inhibiting ACC activity not only alleviates depression-like behaviors but also mitigates CRC-induced neuronal damage and reduces CRC tumor progression. These findings underscore the critical role of the ACC in comorbidity of CRC and depression and suggest that ACC-targeted interventions may hold therapeutic potential for CRC patients with comorbid depression.

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