The nuclear translocation of transketolase inhibits the farnesoid receptor expression by promoting the binding of HDAC3 to FXR promoter in hepatocellular carcinoma cell lines

Li, Minle; Zhang, Xuping; Lu, Ying; Meng, Sen; Quan, Haoyu; Hou, Pingfu; Tong, Pan; Chai, Dafei; Gao, Xiaoge; Zheng, Junnian; Tong, Xuemei; Bai, Jing

doi:10.1038/s41419-020-2225-6

Cited by 26 publications

(16 citation statements)

References 36 publications

(37 reference statements)

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“…For example, in breast cancer, TKT promotes metastasis through regulatingα-Ketoglutarate signaling pathway [ 21 ], and it has been shown that TKT enters the nucleus and activates the EGFR pathway, thereby promoting proliferation, viability, and migration of liver cancer [ 22 ]. Furthermore, our previous research also confirms that TKT transports into the nuclear to inhibit FXR promoter activity, affects liver bile acid metabolism, and promotes liver cancer [ 23 ]. Nevertheless, the function of TKT and related mechanisms in CRC are currently unclear.…”

Section: Introductionmentioning

confidence: 62%

“…To investigate the possible mechanism of TKT in CRC metastasis, we determined the possible genes from the previous mass spectrometry results [ 23 ] and focused on GRP78 because GRP78 promotes tumor growth and migration via regulating AKT phosphorylation [ 26 ]. We suspected that TKT regulated AKT phosphorylation through interacting with GRP78 and then promoted aerobic glycolysis, thereby facilitated CRC cell metastasis.…”

Section: Resultsmentioning

confidence: 99%

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Transketolase promotes colorectal cancer metastasis through regulating AKT phosphorylation

Zhao

Yong

et al. 2022

Cell Death Dis

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Transketolase (TKT) which is an important metabolic enzyme in the pentose phosphate pathway (PPP) participates in maintaining ribose 5-phosphate levels. TKT is necessary for maintaining cell growth. However, we found that in addition to this, TKT can also affect tumor progression through other ways. Our previous study indicate that TKT could promote the development of liver cancer by affecting bile acid metabolism. And in this study, we discovered that TKT expression was remarkably upregulated in colorectal cancer, abnormal high expression of TKT is associated with poor prognosis of colorectal cancer. Additionally, TKT promoted colorectal cancer cell growth and metastasis. Further study demonstrated that TKT interacted with GRP78 and promoted colorectal cancer cell glycolysis through increasing AKT phosphorylation, thereby enhancing colorectal cancer cell metastasis. Thus, TKT is expected to become an indicator for judging the prognosis of colorectal cancer, and provide a theoretical basis for drug development of new treatment targets for colorectal cancer.

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Section: Introductionmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Transketolase promotes colorectal cancer metastasis through regulating AKT phosphorylation

Zhao

Yong

et al. 2022

Cell Death Dis

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“…We further observed that HDAC3 was mainly distributed in the cytoplasm, not the nucleus, in calcified ACP tissue. Considering that HDAC regulates histone acetylation, the distribution of levels inside and outside of the nucleus may affect its function [ 28 , 29 ]. Wang et al [ 22 ] reported that HDAC3 translocation from the cytoplasm into the nucleus was critical for the proliferation and differentiation of oligodendrocyte progenitor cells.…”

Section: Discussionmentioning

confidence: 99%

CBX4-dependent regulation of HDAC3 nuclear translocation reduces Bmp2-induced osteoblastic differentiation and calcification in adamantinomatous craniopharyngioma

et al. 2022

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Background Calcification of adamantinomatous craniopharyngioma (ACP) often causes problems with tumor resection, leading to a high incidence of deadly complications and tumor recurrence. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are 2 key enzymes that regulate histone acetylation and play important roles in tumor development. However, the roles of HAT and HDAC in the calcification and osteoblastic differentiation of ACP are not known. Methods In this study, primary cells were isolated from ACP tissues, and calcification was induced with bone morphogenetic protein 2 (Bmp2). HDAC3 expression was assessed in 12 tissue samples by Western blotting and immunohistochemistry. ACP calcification was assessed by Alizarin red staining. A luciferase reporter assay was performed to examine the interaction between miR-181b and the 3’-untranslated region of the polycomb chromobox 4 (CBX4) gene. Results Our results showed that the expression of HDAC3 was increased in the calcified ACP samples, but inhibition of HDAC3 promoted ACP cell calcification and osteoblastic differentiation. Mechanistically, HDAC3 nuclear translocation was suppressed by Bmp2, leading to Runx2 protein expression and Osterix, osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) mRNA expression. In addition, this process was suppressed by CBX4, which stabilized the nuclear localization of HDAC3. miR-181b, the expression of which was increased in Bmp2-induced ACP cells, directly targeted and decreased CBX4 expression and inhibited the nuclear localization of HDAC3. Conclusions Our results demonstrate that Bmp2 increases miR-181b levels to directly target and inhibit CBX4 expression, leading to a reduction in the CBX4-dependent regulation of HDAC3 nuclear translocation, which results in Runx2 activation/osteoblastic differentiation and calcium deposition in ACP. Further studies targeting these cascades may contribute to therapeutic interventions used for recurrent ACP.

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“…Studies on metastatic ovarian cancer have shown ( 19 ) that inhibiting TKT expression blocks the proliferation of the SKOV-3 cell line, which is an ovarian cancer cell line, and that oxythiamine, an inhibitor of TKT activity, significantly inhibits the proliferation of four ovarian cancer cell lines and primary serous ovarian cancer cells isolated from the patient’s ascites. Li et al ( 35 ) studied the relationship between TKT expression and bile acid levels in mouse liver cancer tissues. The results showed that TKT is transported to the nuclei of liver cancer cells by interacting with the signal transducer and activator of transcription-1 (STAT-1).…”

Section: Discussionmentioning

confidence: 99%

A Correlative Study Between IVIM-DWI Parameters and the Expression Levels of Ang-2 and TKT in Hepatocellular Carcinoma

et al. 2021

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BackgroundNoninvasive evaluation of the expression of angiopoietin-2 (Ang-2) and transketolase (TKT) in hepatocellular carcinoma (HCC) is of great significance for the clinical development of individualized treatment plans. However, the correlation between intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and the expression of Ang-2 and TKT has not been reported. We sought to investigate the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs.MethodsConventional non-enhanced magnetic resonance imaging (MRI) and IVIM-DWI and dynamic contrast MRI were performed for 61 patients with HCC before surgical treatment. Various IVIM-DWI parameters, such as apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*) and fraction of fast apparent diffusion coefficient (f), were calculated using Function-MADC software. Expression levels of Ang-2 and TKT in HCC were detected via immunohistochemical staining and classified into two grades. Independent sample t tests were used to compare differences in parameters between the two groups. The Spearman rank correlation test was used to analyze the correlations between IVIM-DWI parameters and Ang-2 and TKT expression levels in HCCs.ResultsThe D* and f values were significantly higher in the high Ang-2 group than in the low Ang-2 group; there were no obvious between-group differences in ADC and D. Ang-2 expression was positively correlated with D* and f but not with ADC and D. The ADC and D values were significantly lower in the high TKT group than in the low TKT group, whereas the between-group differences for D* and f were not significant. TKT expression was negatively correlated with ADC and D but not with D* and f.ConclusionsIVIM-DWI can be used to evaluate Ang-2 and TKT expression in HCC.

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The nuclear translocation of transketolase inhibits the farnesoid receptor expression by promoting the binding of HDAC3 to FXR promoter in hepatocellular carcinoma cell lines

Cited by 26 publications

References 36 publications

Transketolase promotes colorectal cancer metastasis through regulating AKT phosphorylation

Transketolase promotes colorectal cancer metastasis through regulating AKT phosphorylation

CBX4-dependent regulation of HDAC3 nuclear translocation reduces Bmp2-induced osteoblastic differentiation and calcification in adamantinomatous craniopharyngioma

A Correlative Study Between IVIM-DWI Parameters and the Expression Levels of Ang-2 and TKT in Hepatocellular Carcinoma

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