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

Chu, Tian‐Huei; Ko, C. M.; Tai, Po-Han; Chang, Yu‐Chan; Huang, Chao‐Cheng; Wu, Tung-Yang; Chan, Hoi‐Hung; Wu, Ping-Hsuan; Weng, Chien-Hui; Lin, Yu‐Wei; Kung, Mei-Lang; Fang, Cheng-Chieh; Wu, Jian-Ching; Wen, Zhi‐Hong; Lee, Yung-Kuo; Hu, Tsung–Hui; Tai, Ming‐Hong

doi:10.1016/j.jbc.2022.102442

Cited by 6 publications

(4 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our group revealed that LECT2 interacts with Trf, and this interaction is highly conserved from fish to mouse (45). 4 The roles LECT2 in immune diseases 4.1 Tumor immunity LECT2 functions as a tumor suppressor in many cancers (5,46,48,(51)(52)(53). Apart from directly interacting with cancer cells, LECT2 also modulates cancer progression via the tumor immune microenvironment (TIM) (51,52).…”

Section: Lect2-mediated Signalingmentioning

confidence: 99%

“…LECT2 functions as a tumor suppressor in many cancers ( 5 , 46 , 48 , 51 – 53 ). Apart from directly interacting with cancer cells, LECT2 also modulates cancer progression via the tumor immune microenvironment (TIM) ( 51 , 52 ).…”

Section: The Roles Lect2 In Immune Diseasesmentioning

confidence: 99%

“…CD209a is the first identified LECT2 receptor discovered by our group (41), and it contributes to enhancing the bacterial clearance ability of macrophages by phosphorylating the c-Jun N-terminal kinase (JNC) (Figure 2A) (22,41). c-Met is the other receptor of LECT2, and the c-Met-LECT2 protein-protein interaction (PPI) impedes MET receptor activation to inhibit vascular invasion, metastasis, proliferation, and stemness of cancers by antagonizing different cancer activation pathways (Figure 2B) (43,(46)(47)(48). In addition, Shirasaki et al found that LECT2 functions as an anti-viral protein against lymphocytic choriomeningitis virus (LCMV) by binding to c-Met and thus competes with HGF-MET signaling (Figure 2B) (42).…”

Section: Lect2-mediated Signalingmentioning

confidence: 99%

See 2 more Smart Citations

The emerging roles of leukocyte cell-derived chemotaxin-2 in immune diseases: From mechanisms to therapeutic potential

Zhu

Liu²,

Li³

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Leukocyte cell-derived chemotaxin-2 (LECT2, also named ChM-II), initially identified as a chemokine mediating neutrophil migration, is a multifunctional secreted factor involved in diverse physiological and pathological processes. The high sequence similarity of LECT2 among different vertebrates makes it possible to explore its functions by using comparative biology. LECT2 is associated with many immune processes and immune-related diseases via its binding to cell surface receptors such as CD209a, Tie1, and Met in various cell types. In addition, the misfolding LECT2 leads to the amyloidosis of several crucial tissues (kidney, liver, and lung, etc.) by inducing the formation of insoluble fibrils. However, the mechanisms of LECT2-mediated diverse immune pathogenic conditions in various tissues remain to be fully elucidated due to the functional and signaling heterogeneity. Here, we provide a comprehensive summary of the structure, the “double-edged sword” function, and the extensive signaling pathways of LECT2 in immune diseases, as well as the potential applications of LECT2 in therapeutic interventions in preclinical or clinical trials. This review provides an integrated perspective on the current understanding of how LECT2 is associated with immune diseases, with the aim of facilitating the development of drugs or probes against LECT2 for the theranostics of immune-related diseases.

show abstract

Section: Lect2-mediated Signalingmentioning

confidence: 99%

Section: The Roles Lect2 In Immune Diseasesmentioning

confidence: 99%

Section: Lect2-mediated Signalingmentioning

confidence: 99%

See 1 more Smart Citation

The emerging roles of leukocyte cell-derived chemotaxin-2 in immune diseases: From mechanisms to therapeutic potential

Zhu

Liu²,

Li³

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Leukocyte cell-derived chemotaxin 2 (LECT2) is a recently discovered hepatokine that plays crucial roles in various diseases, such as obesity [ 61 ], T2D [ 62 ], liver fibrosis [ 63 ], and hepatocellular carcinoma [ 64 ]. Studies have reported that hepatic and serum levels of LECT2 are known to be strongly associated with BMI and liver fat in humans [ 62 ] and mice [ 65 ].…”

Section: Hepatokinesmentioning

confidence: 99%

The Role of Organokines in Obesity and Type 2 Diabetes and Their Functions as Molecular Transducers of Nutrition and Exercise

Lim,

Kim

2023

Metabolites

View full text Add to dashboard Cite

Maintaining systemic homeostasis requires the coordination of different organs and tissues in the body. Our bodies rely on complex inter-organ communications to adapt to perturbations or changes in metabolic homeostasis. Consequently, the liver, muscle, and adipose tissues produce and secrete specific organokines such as hepatokines, myokines, and adipokines in response to nutritional and environmental stimuli. Emerging evidence suggests that dysregulation of the interplay of organokines between organs is associated with the pathophysiology of obesity and type 2 diabetes (T2D). Strategies aimed at remodeling organokines may be effective therapeutic interventions. Diet modification and exercise have been established as the first-line therapeutic intervention to prevent or treat metabolic diseases. This review summarizes the current knowledge on organokines secreted by the liver, muscle, and adipose tissues in obesity and T2D. Additionally, we highlighted the effects of diet/nutrition and exercise on the remodeling of organokines in obesity and T2D. Specifically, we investigated the ameliorative effects of caloric restriction, selective nutrients including ω3 PUFAs, selenium, vitamins, and metabolites of vitamins, and acute/chronic exercise on the dysregulation of organokines in obesity and T2D. Finally, this study dissected the underlying molecular mechanisms by which nutrition and exercise regulate the expression and secretion of organokines in specific tissues.

show abstract

Sodium‐Glucose Co‐Transporter‐2 Inhibitor Empagliflozin Attenuates Sorafenib‐Induced Myocardial Inflammation and Toxicity

Liu,

Ho,

Lee

et al. 2024

Environmental Toxicology

View full text Add to dashboard Cite

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real‐time quantitative RT‐PCR (qRT‐PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib‐treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28‐day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib‐induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT‐dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib‐treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib‐promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib‐stimulated proinflammatory signaling (TNF‐α/IL‐1β/IL‐6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib‐promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

show abstract

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

Cited by 6 publications

References 57 publications

The emerging roles of leukocyte cell-derived chemotaxin-2 in immune diseases: From mechanisms to therapeutic potential

The emerging roles of leukocyte cell-derived chemotaxin-2 in immune diseases: From mechanisms to therapeutic potential

The Role of Organokines in Obesity and Type 2 Diabetes and Their Functions as Molecular Transducers of Nutrition and Exercise

Sodium‐Glucose Co‐Transporter‐2 Inhibitor Empagliflozin Attenuates Sorafenib‐Induced Myocardial Inflammation and Toxicity

Contact Info

Product

Resources

About