2. Academic Validation
  3. HOXC8-activated TRIM22/NF-κB pathway promotes stemness in colorectal cancer

HOXC8-activated TRIM22/NF-κB pathway promotes stemness in colorectal cancer

  • Cancer Lett. 2026 Jan 28:638:218156. doi: 10.1016/j.canlet.2025.218156.
Song Tan 1,  Yifan Chen 1,  Yizhen Chen 2,  Shaolin Liu 1,  Changshun Yang 3,  Yulong Mi 4,  Xiaojun Lin 1,  Houqiang Li 5,  Hengrui Liu 6,  Weihua Li 7,  Shengtao Lin 8
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, No.134, Dongjie, Fuzhou, 350001, China; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350013, China.
  • 2 Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350013, China; Department of Thoracic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, 350001, China; Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350004, China.
  • 3 Department of Gastrointestinal Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, No.134, Dongjie, Fuzhou, 350001, China; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350013, China; Department of Thoracic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, 350001, China.
  • 4 Department of Gastrointestinal Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, No.134, Dongjie, Fuzhou, 350001, China; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350013, China; Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350004, China.
  • 5 Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350013, China; Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350004, China.
  • 6 Department of Biochemistry, University of Cambridge, UK. Electronic address: [email protected].
  • 7 Department of Gastrointestinal Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, No.134, Dongjie, Fuzhou, 350001, China; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350013, China; Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350004, China. Electronic address: [email protected].
  • 8 Department of Gastrointestinal Surgery, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital, No.134, Dongjie, Fuzhou, 350001, China; Shengli Clinical Medical College of Fujian Medical University, Fuzhou, 350013, China; Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350004, China. Electronic address: [email protected].
PMID: 41265630 DOI: 10.1016/j.canlet.2025.218156
Abstract

Colorectal Cancer (CRC) remains a significant global health challenge and is characterized by high incidence and mortality rates. Although the homeobox gene family has been implicated in oncogenic processes, the precise functional role of HOXC8 in regulating CRC proliferation and stemness remains poorly defined. Cancer cells with stem-related properties, a distinct cellular subpopulation endowed with self-renewal and differentiation capacities, play pivotal roles in tumor initiation, metastasis, and therapeutic resistance. In this study, we demonstrate that HOXC8 overexpression promotes CRC cell proliferation, enhances stemness properties, and confers chemoresistance. Mechanistically, HOXC8 transcriptionally activates TRIM22, leading to the ubiquitination and degradation of IκBα, which subsequently potentiates NF-κB signaling to drive stemness maintenance in CRC cells. These findings delineate a previously unrecognized HOXC8/TRIM22/NF-κB signaling axis that critically regulates tumor progression, offering a promising molecular target for therapeutic intervention in CRC.

Keywords

Colorectal cancer; HOXC8; NF-κB; Stemness; Ubiquitination.

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