AKAP12 promotes cancer stem cell-like phenotypes and activates STAT3 in colorectal cancer

• Ke Li ^[1] ; Xuan Wu ^[1] ; Yuan Li ^[3] ; Ting-Ting Hu ^[4] ; Weifeng Wang ^[1] ; Frank J. Gonzalez ^[2] ; Weiwei Liu ^[1]
  1. [1] Shanghai University of Traditional Chinese Medicine

     Shanghai University of Traditional Chinese Medicine

     China

     
  2. [2] National Institutes of Health

     National Institutes of Health

     Estados Unidos

     
  3. [3] Department of Laboratory Medicine, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai, 200070, People’s Republic of China
  4. [4] Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, People’s Republic of China

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 25, Nº. 11 (November), 2023, págs. 3263-3276
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • Background Cancer stem cells (CSCs) have unique biological characteristics, including tumorigenicity, immortality, and chemoresistance. Colorectal CSCs have been identified and isolated from colorectal cancers by various methods. AKAP12, a scaffolding protein, is considered to act as a potential suppressor in colorectal cancer, but its role in CSCs remains unknown. In this study, we investigated the function of AKAP12 in Colorectal CSCs.

    Methods Herein, Colorectal CSCs were enriched by cell culture with a serum-free medium. CSC-associated characteristics were evaluated by Flow cytometry assay and qPCR. AKAP12 gene expression was regulated by lentiviral transfection assay. The tumorigenicity of AKAP12 in vivo by constructing a tumor xenograft model. The related pathways were explored by qPCR and Western blot.

    Results The depletion of AKAP12 reduced colony formation, sphere formation, and expression of stem cell markers in colorectal cancer cells, while its knockdown decreased the volume and weight of tumor xenografts in vivo. AKAP12 expression levels also affected the expression of stemness markers associated with STAT3, potentially via regulating the expression of protein kinase C.

    Conclusion This study suggests Colorectal CSCs overexpress AKAP12 and maintain stem cell characteristics through the AKAP12/PKC/STAT3 pathway. AKAP12 may be an important therapeutic target for blocking the development of colorectal cancer in the field of cancer stem cells.