Choline transporter-like protein 1 in tongue squamous cell carcinoma: implications for cell proliferation and differentiation

Sci Rep. 2025 Aug 29;15(1):31927. doi: 10.1038/s41598-025-17702-x.

Abstract

Studies have indicated moderate to high choline transporter-like protein 1 (CTL1) expression in colon, pancreatic, breast, lung, and glioma cancers. However, studies on CTL1 in oral squamous cell carcinoma (OSCC), a highly invasive cancer, remain limited. We aimed to investigate the expression and localization of CTL1 in OSCC and its association with cell proliferation. Using in vitro experiments, we evaluated CTL1 expression and localization in the OSCC cell lines HSC-3 and HSC-4 by immunocytochemistry and western blotting. A cell proliferation assay was performed using hemicolinium-3, a choline uptake inhibitor. Using in vivo and ex vivo experiments, we assessed CTL1 expression in rat and human tongue cancer tissues by immunohistochemical and immunofluorescent staining. Here, we show that CTL1 is strongly expressed intracellularly and localized in organelles of HSC-3 and HSC-4 cells. CTL1 significantly accumulated around the nucleus in Ki67-positive cells with proliferative potential, suggesting increased production and transport of CTL1. Conversely, the number of cells in the HC-3 treated group in both HSC-3 and HSC-4 cells decreased. These results suggest that intracellular production of CTL1 is further increased in Ki67-positive cells, and choline uptake may lead to cell proliferation. In vivo and ex vivo experiments revealed high CTL1 expression in tongue cancer, with stronger expression in well-differentiated tumors than that in poorly-differentiated ones. Our study demonstrates that CTL1 is associated with OSCC proliferation and tumor differentiation. These findings suggest that CTL1 may function as a potential marker for tumor differentiation and progression of OSCC.

MeSH terms

  • Animals
  • Antigens, CD
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / metabolism
  • Carcinoma, Squamous Cell* / pathology
  • Cell Differentiation*
  • Cell Line, Tumor
  • Cell Proliferation
  • Choline / metabolism
  • Gene Expression Regulation, Neoplastic
  • Hemicholinium 3 / pharmacology
  • Humans
  • Male
  • Organic Cation Transport Proteins* / metabolism
  • Rats
  • Tongue Neoplasms* / genetics
  • Tongue Neoplasms* / metabolism
  • Tongue Neoplasms* / pathology

Substances

  • Choline
  • SLC44A1 protein, human
  • Organic Cation Transport Proteins
  • Hemicholinium 3
  • Antigens, CD