Tyrosine metabolic enzyme HPD is decreased and predicts unfavorable outcomes in hepatocellular carcinoma

Yang, Xia; Chen, Shi-Lu; Lin, Cen-Shan; Liu, Li‐Li; Wang, Chunhua; Yun, Jing‐Ping

doi:10.1016/j.prp.2020.153153

Cited by 10 publications

(8 citation statements)

References 20 publications

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“…4(c,d), remarkable reduction of fluorescence was observed with the increase of NTBC dosage. Notably, the fluorescence signal in zebrafish was mainly distributed in the liver, which is consistent with the previous report that HPPD is highly expressed in liver 53 . Considering the wide application of HPPD inhibitors as herbicides, we expect that HP‐1 could provide a simple but reliable tool for analyzing HPPD herbicide contaminants in mammals and other species.…”

Section: Resultssupporting

confidence: 89%

In vivo fluorescent screening for HPPD‐targeted herbicide discovery

Zhang

Guo

et al. 2022

Pest Management Science

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Background 4‐Hydroxyphenylpyruvate dioxygenase (HPPD), playing a critical role in vitamin E and plastoquinone biosynthesis in plants, has been recognized as one of the most important targets for herbicide discovery for over 30 years. Structure‐based rational design of HPPD inhibitors has received more and more research interest. However, a critical challenge in the discovery of new HPPD inhibitors is the common inconsistency between molecular‐level HPPD‐based bioevaluation and the weed control efficiency in fields, due to the unpredictable biological processes of absorption, distribution, metabolism, and excretion. Results In this study, we developed a fluorescent‐sensing platform of efficient in vivo screening for HPPD‐targeted herbicide discovery. The refined sensor has good capability of in situ real‐time fluorescence imaging of HPPD in living cells and zebrafish. More importantly, it enabled the direct visible monitoring of HPPD inhibition in plants in a real‐time manner. Conclusion We developed a highly efficient in vivo fluorescent screening method for HPPD‐targeted herbicide discovery. This discovery not only offers a promising tool to advance HPPD‐targeted herbicide discovery, but it also demonstrates a general path to develop the highly efficient, target‐based, in vivo screening for pesticide discovery. © 2022 Society of Chemical Industry.

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Section: Resultssupporting

confidence: 89%

In vivo fluorescent screening for HPPD‐targeted herbicide discovery

Zhang

Guo

et al. 2022

Pest Management Science

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“…We found that the expression of tyrosine aminotransferase (TAT), HPD, homogentisate 1,2-dioxygenase (HGD), GSTZ1, and FAH at mRNA level was significantly decreased in HCC ( Figure 1 E,F). The expressions of HPD and GSTZ1 were found to be significantly down-regulated in the HCC patients collected in the reported articles [ 4 , 25 ]. Taken together, these findings suggest that the tyrosine metabolism pathway is significantly inhibited in HCC and may play a crucial role in HCC development.…”

Section: Resultsmentioning

confidence: 99%

Decreased SLC27A5 Suppresses Lipid Synthesis and Tyrosine Metabolism to Activate the Cell Cycle in Hepatocellular Carcinoma

et al. 2022

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Tyrosine is an essential ketogenic and glycogenic amino acid for the human body, which means that tyrosine is not only involved in protein metabolism, but also participates in the metabolism of lipids and carbohydrates. The liver is an important place for metabolism of lipids, carbohydrates, and proteins. The metabolic process of biological macro-molecules is a basis for maintaining the physiological activities of organisms, but the cross-linking mechanism of these processes is still unclear. Here, we found that the tyrosine-metabolizing enzymes, which were specifically and highly expressed in the liver, were significantly down-regulated in hepatocellular carcinoma (HCC), and had a correlation with a poor prognosis of HCC patients. Further analysis found that the reduction of tyrosine metabolism would activate the cell cycle and promote cell proliferation. In addition, we also found that the solute carrier family 27 member 5 (SLC27A5) regulates the expression of tyrosine-metabolizing enzymes through nuclear factor erythroid 2-related factor 2 (NRF2). Therefore, the SLC27A5 and tyrosine-metabolizing enzymes that we have identified coordinate lipid and tyrosine metabolism, regulate the cell cycle, and are potential targets for cancer treatment.

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“…In patients with chronic liver diseases, an upregulation of serum tyrosine levels has been previously reported (Tajiri and Shimizu, 2013). Deregulation of tyrosine catabolic enzymes has been independently reported in various types of cancers, including HCC (Shan et al, 2019;Wang et al, 2019;Fu et al, 2010;Li et al, 2019;Orejuela et al, 2008;Yang et al, 2019Yang et al, , 2020. Our group has recently reported that loss of the second tyrosine catabolic enzyme HPD is closely associated with poor clinical outcome in HCC (Yang et al, 2020).…”

Section: Introductionmentioning

confidence: 66%

“…Deregulation of tyrosine catabolic enzymes has been independently reported in various types of cancers, including HCC (Shan et al, 2019;Wang et al, 2019;Fu et al, 2010;Li et al, 2019;Orejuela et al, 2008;Yang et al, 2019Yang et al, , 2020. Our group has recently reported that loss of the second tyrosine catabolic enzyme HPD is closely associated with poor clinical outcome in HCC (Yang et al, 2020). However, the metabolic consequences of disordered tyrosine catabolism in association with the rewiring of nutrient reliance and adaptation to drive hepatic tumorigenesis remain poorly characterized.…”

Section: Introductionmentioning

confidence: 89%

“…To examine the functional and metabolic consequences of impaired tyrosine catabolism, we manipulated the expression and activity of the second tyrosine catabolic enzyme, HPD, of which we recently reported its clinical importance in human HCC (Yang et al, 2020). We examined HPD expression in a panel of normal liver and liver cancer cell lines (Figure 2A).…”

Section: Hpd Silencing Promotes Cell Proliferation and Tumorigenesismentioning

confidence: 99%

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Loss of tyrosine catabolic enzyme HPD promotes glutamine anaplerosis through mTOR signaling in liver cancer

et al. 2021

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Tyrosine metabolic enzyme HPD is decreased and predicts unfavorable outcomes in hepatocellular carcinoma

Cited by 10 publications

References 20 publications

In vivo fluorescent screening for HPPD‐targeted herbicide discovery

In vivo fluorescent screening for HPPD‐targeted herbicide discovery

Decreased SLC27A5 Suppresses Lipid Synthesis and Tyrosine Metabolism to Activate the Cell Cycle in Hepatocellular Carcinoma

Loss of tyrosine catabolic enzyme HPD promotes glutamine anaplerosis through mTOR signaling in liver cancer

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