2. Academic Validation
  3. SMYD3 synergises with RACK1 to promote colorectal cancer lung metastasis by recruiting SMAD3

SMYD3 synergises with RACK1 to promote colorectal cancer lung metastasis by recruiting SMAD3

  • Cell Commun Signal. 2026 Feb 3;24(1):156. doi: 10.1186/s12964-026-02687-5.
Xiaoming Bai # 1,  Dong Han # 2,  Jie Chen # 2,  Siqi Sheng 2,  Haimei Feng 1,  Hongyu Wang 1,  Ke Xu 2,  Yadi Huang 3,  Mengxi Huang 4,  Xiaoyuan Chu 5 6 7 8,  Yitian Chen 9 10,  Zengjie Lei 11 12 13 14
Affiliations

Affiliations

  • 1 Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
  • 2 Department of Medical Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, Jiangsu Province, 210000, China.
  • 3 Department of Medical Oncology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu Province, China.
  • 4 Department of Medical Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, Jiangsu Province, 210000, China. [email protected].
  • 5 Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. [email protected].
  • 6 Department of Medical Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, Jiangsu Province, 210000, China. [email protected].
  • 7 Department of Medical Oncology, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China. [email protected].
  • 8 Department of Medical Oncology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu Province, China. [email protected].
  • 9 Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. [email protected].
  • 10 Department of Medical Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, Jiangsu Province, 210000, China. [email protected].
  • 11 Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. [email protected].
  • 12 Department of Medical Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, Jiangsu Province, 210000, China. [email protected].
  • 13 Department of Medical Oncology, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China. [email protected].
  • 14 Department of Medical Oncology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu Province, China. [email protected].
  • # Contributed equally.
PMID: 41634833 DOI: 10.1186/s12964-026-02687-5
Abstract

Cancer metastasis is the leading cause of mortality associated with Cancer, and the prognosis for patients diagnosed with colorectal Cancer(CRC) largely depends on the occurrence of metastasis during the progression of the disease. A comprehensive understanding of the mechanisms underlying metastasis in CRC is essential for advancing treatment strategies. Through integrated bioinformatics analysis of mRNA expression profiles and epigenetic modifiers, we identified SMYD3 as the top differentially expressed histone modifier in CRC. Clinically, SMYD3 overexpression significantly associates with poor prognosis and enhances metastatic potential. Utilizing immunoprecipitation-mass spectrometry, we discovered RACK1 as a novel SMYD3-interacting protein. Subsequent mechanistic studies revealed a tripartite interaction network: SMYD3 recruits SMAD3 through RACK1-mediated scaffolding, facilitating transcriptional activation of the downstream effector TSKU. Notably, RACK1 depletion disrupts SMYD3-SMAD3 complex formation, establishing the critical role of this axis in metastasis regulation. Consequently, inhibiting the SMYD3-SMAD3 interaction may represent a promising therapeutic strategy for addressing CRC metastasis. In conclusion, targeting the SMYD3-RACK1-SMAD3 transcriptional complex presents a viable approach for the treatment of CRC metastasis.

Keywords

Colorectal cancer; Metastasis; RACK1; SMAD3; SMYD3.

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