Leukocyte cell-derived chemotaxin 2 regulates epithelial-mesenchymal transition and cancer stemness in hepatocellular carcinoma

Tian Huei Chu, Chou Yuan Ko, Po Han Tai, Yi Chen Chang, Chao Cheng Huang, Tung Yang Wu, Hoi Hung Chan, Ping Hsuan Wu, Chien Hui Weng, Yu Wei Lin, Mei Lang Kung, Cheng Chieh Fang, Jian Ching Wu, Zhi Hong Wen, Yung Kuo Lee, Tsung Hui Hu*, Ming Hong Tai

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

4 Scopus citations


Leukocyte cell-derived chemotaxin 2 (LECT2) acts as a tumor suppressor in hepatocellular carcinoma (HCC). However, the antineoplastic mechanism of LECT2, especially its influence on hepatic cancer stem cells (CSCs), remains largely unknown. In The Cancer Genome Atlas cohort, LECT2 mRNA expression was shown to be associated with stage, grade, recurrence, and overall survival in human HCC patients, and LECT2 expression was downregulated in hepatoma tissues compared with the adjacent nontumoral liver. Here, we show by immunofluorescence and immunoblot analyses that LECT2 was expressed at lower levels in tumors and in poorly differentiated HCC cell lines. Using functional assays, we also found LECT2 was capable of suppressing oncogenic behaviors such as cell proliferation, anchorage-independent growth, migration, invasiveness, and epithelial-mesenchymal transition in hepatoma cells. Moreover, we show exogenous LECT2 treatment inhibited CSC functions such as tumor sphere formation and drug efflux. Simultaneously, hepatic CSC marker expression was also downregulated, including expression of CD133 and CD44. This was supported by infection with adenovirus encoding LECT2 (Ad-LECT2) in HCC cells. Furthermore, in animal experiments, Ad-LECT2 gene therapy showed potent efficacy in treating HCC. We demonstrate LECT2 overexpression significantly promoted cell apoptosis and reduced neovascularization/CSC expansion in rat hepatoma tissues. Mechanistically, we showed using immunoblot and immunofluorescence analyses that LECT2 inhibited β-catenin signaling via the suppression of the hepatocyte growth factor/c-MET axis to diminish CSC properties in HCC cells. In summary, we reveal novel functions of LECT2 in the suppression of hepatic CSCs, suggesting a potential alternative strategy for HCC therapy.

Original languageEnglish
Article number102442
JournalJournal of Biological Chemistry
Issue number10
StatePublished - 10 2022

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  • cancer stem cells
  • epithelial-mesenchymal transition
  • hepatocellular carcinoma
  • leukocyte cell-derived chemotaxin 2
  • prognostic biomarker


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