Hexokinase 2 Promotes Cell Proliferation and Tumor Formation through the Wnt/β-catenin Pathway-mediated Cyclin D1/c-myc Upregulation in Epithelial Ovarian Cancer

Liu, Xian; Zuo, Xiaohang; Sun, Xiaoli; Tian, Xueye; Teng, Yue

doi:10.7150/jca.71894

Cited by 22 publications

(12 citation statements)

References 29 publications

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“…In general, activation of the Wnt/β-catenin signaling pathway induces transcription of genes associated with cell proliferation . It has been shown that Gln deficiency leads to impairment of the Wnt/β-catenin pathway and diminished protein synthesis, thereby affecting the growth of oligodendrocytes, which is similar to our results.…”

Section: Discussionsupporting

confidence: 91%

“…In general, activation of the Wnt/β-catenin signaling pathway induces transcription of genes associated with cell proliferation. 40 It has been shown that Gln deficiency leads to impairment of the Wnt/β-catenin pathway and diminished protein synthesis, thereby affecting the growth of oligodendrocytes, 16 which is similar to our results. Gln evidently enhanced the expression of β-catenin, active-β-catenin, TCF4, c-Myc, and cyclin D1, thus waking the Wnt/β-catenin pathway in IPEC-J2 cells.…”

Section: ■ Discussionsupporting

confidence: 90%

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Glutamine Promotes Porcine Intestinal Epithelial Cell Proliferation through the Wnt/β-Catenin Pathway

Fang,

Lu,

Cheng

et al. 2024

J. Agric. Food Chem.

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Glutamine (Gln) is a critical nutrient required by neonatal mammals for intestinal growth, especially for newborn piglets. However, the mechanisms underlying the role of Gln in porcine intestinal epithelium development are not fully understood. The objective of the current study was to explore the possible signaling pathway involved in the promotion of porcine intestinal epithelial cell (IPEC-J2) proliferation by Gln. The results showed that 1 mM Gln promoted IPEC-J2 cell proliferation, and tandem mass tag proteomics revealed 973 differentially expressed proteins in Gln-treated IPEC-J2 cells, 824 of which were upregulated and 149 of which were downregulated. Moreover, gene set enrichment analysis indicated that the Wnt signaling pathway is activated by Gln treatment. Western blotting analysis further confirmed that Gln activated the Wnt/β-catenin signaling pathway. In addition, Gln increased not only cytosolic β-catenin but also nuclear β-catenin protein expression. LF3 (a β-catenin/TCF4 interaction inhibitor) assay and β-catenin knockdown demonstrated that Gln-mediated promotion of Wnt/β-catenin signaling and cell proliferation were blocked. Furthermore, the inhibition of TCF4 expression suppressed Gln-induced cell proliferation. These findings further confirmed that Wnt/β-catenin signaling is involved in the promotion of IPEC-J2 cell proliferation by Gln. Collectively, these findings demonstrated that Gln positively regulated IPEC-J2 cell proliferation through the Wnt/β-catenin pathway. These data greatly enhance the current understanding of the mechanism by which Gln regulates intestinal development.

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Section: Discussionsupporting

confidence: 91%

Section: ■ Discussionsupporting

confidence: 90%

Glutamine Promotes Porcine Intestinal Epithelial Cell Proliferation through the Wnt/β-Catenin Pathway

Fang,

Lu,

Cheng

et al. 2024

J. Agric. Food Chem.

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“…The Immunohistochemistry used in this study were performed as previously described [ 31 ]. The staining intensity was scored as: 0 (no staining), 1 (light brown), 2 (brown), 3 (dark brown).…”

Section: Methodsmentioning

confidence: 99%

Hexokinase 2 promoted cell motility and proliferation by activating Akt1/p-Akt1 in human ovarian cancer cells

et al. 2022

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Background Recently, increasing evidence has indicated that elevation of Hexokinase 2 (HK2) plays an important role in several cancers on regulating cell motility and growth. However, its role on regulating cell EMT in human ovarian cancer still less to known. Methods The transwell and wound-healing assay were used to detect the effective of HK2 on regulating motility of ovarian cancer cells. Real Time PCR and Western Blotting were used to explore the changing of EMT-related proteins in HK2-modified cells. The clonogenic formation, cell growth curves and MTT assays were used to evaluate the effective of HK2 on regulating cell proliferation in HK2-modified cells. The flow cytometry was used to detect the differences in the distribution of cells in the cell cycle between the HK2-modified cells and their control cells. The correlation of HK2 and Akt1/p-Akt1 was explored by using Western Blotting, Akt1 inhibitor (MK2206) and transient transfection of an Akt1 recombinant plasmid. The potential correlation between HK2 and EMT-related proteins in human ovarian cancer tissues and OV (ovarian serous cystadenocarcinoma) was confirmed by using Pearson correlation analysis and TIMER 2.0. Results In ovarian cancer cells, overexpressing of HK2 enhanced cell motility by inducing of EMT-related proteins, such as CDH2, fibronectin, MMP9, ZEB1, ZEB2 and vimentin. Moreover, overexpressing of HK2 promoted cell growth by reducing p21 and p27 expression in ovarian cancer cells. Further studies demonstrated that this promotion of cell motility and growth by HK2 was probably a result of it activating of Akt1 (p-Akt1) in ovarian cancer cells. Additionally, the positive correlation between HK2 and p-Akt1, fibronectin, MMP9 expression in human ovarian cancer samples was verified by using Pearson correlation analysis. The positive correlation between HK2 and CDH2, fibronectin, MMP9, ZEB1, ZEB2 and vimentin in OV (ovarian serous cystadenocarcinoma) was confirmed by using TIMER 2.0. Conclusion This study demonstrated that HK2 could induce EMT-related proteins and reduce cell cycle inhibitor by activating Akt1 in human ovarian cancer cells, subsequently enhancing cell motility and growth, suggesting that HK2 participate in the malignant process of ovarian cancer by interacting with Akt1.

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“…Oncogenic signaling pathways, such as phosphoinositide 3-kinase (PI3K)/AKT, Myc, and the Hippo pathway mediated upregulation and hyperactivation of metabolism-related genes [ 70 ]. K-Ras and c-Myc are responsible for increased glycolysis [ 71 , 72 ]. PIK3CA and ubiquitin-specific peptidase 13 (USP13) genes have been reported to be co-amplified in about 30% of HGSC [ 73 ].…”

Section: Resultsmentioning

confidence: 99%

Recent advances in understanding the metabolic plasticity of ovarian cancer: A systematic review

Kobayashi¹

2022

Heliyon

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Hexokinase 2 Promotes Cell Proliferation and Tumor Formation through the Wnt/β-catenin Pathway-mediated Cyclin D1/c-myc Upregulation in Epithelial Ovarian Cancer

Cited by 22 publications

References 29 publications

Glutamine Promotes Porcine Intestinal Epithelial Cell Proliferation through the Wnt/β-Catenin Pathway

Glutamine Promotes Porcine Intestinal Epithelial Cell Proliferation through the Wnt/β-Catenin Pathway

Hexokinase 2 promoted cell motility and proliferation by activating Akt1/p-Akt1 in human ovarian cancer cells

Recent advances in understanding the metabolic plasticity of ovarian cancer: A systematic review

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