LHPP Inhibits the Proliferation and Metastasis of Renal Cell Carcinoma

Zhang, Xiaoting; Kang, Huaning; Xiao, Jing; Shi, Benyan; Li, Xiaofeng; Chen, Guihong

doi:10.1155/2020/7020924

Cited by 20 publications

(11 citation statements)

References 14 publications

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“…The results in Figure j and Table S6 show that the Arg biosynthesis pathways (Figure S22a), Arg and proline metabolism pathways (Figure S22b), His metabolism pathways (Figure S22c), and vitamin B6 metabolism pathways (Figure S22d) are mapped, suggesting the relation of these pathways to RCC. These are consistent with the previous reports. − …”

Section: Resultssupporting

confidence: 94%

Diagnosing, Typing, and Staging of Renal Cell Carcinoma by Designer Matrix-Based Urinary Metabolic Analysis

Wang

Chen

et al. 2022

Anal. Chem.

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Molecular diagnosing, typing, and staging have been considered to be the ideal alternatives of imaging-based detection methods in clinics. Designer matrix-based analytical tools, with high speed, throughout, efficiency and low/noninvasiveness, have attracted much attention recently for in vitro metabolite detection. Herein, we develop an advanced metabolic analysis tool based on highly porous metal oxides derived from available metal–organic frameworks (MOFs), which elaborately inherit the morphology and porosity of MOFs and newly incorporate laser adsorption capacity of metal oxides. Through optimized conditions, direct high-quality fingerprinting spectra in 0.5 μL of urine are acquired. Using these fingerprinting spectra, we can discriminate the renal cell carcinoma (RCC) from healthy controls with higher than 0.99 of area under the curve (AUC) values (R 2 Y(cum) = 0.744, Q 2 (cum) = 0.880), as well, from patients with other tumors (R 2 Y(cum) = 0.748, Q 2(cum) = 0.871). We also realize the typing of three RCC subtypes, including clear cell RCC, chromophobe RCC (R 2 Y(cum) = 0.620, Q 2(cum) = 0.656), and the staging of RCC (R 2 Y(cum) = 0.755, Q 2(cum) = 0.857). Moreover, the tumor sizes (threshold value is 3 cm) can be remarkably recognized by this advanced metabolic analysis tool (R 2 Y(cum) = 0.710, Q 2(cum) = 0.787). Our work brings a bright prospect for designer matrix-based analytical tools in disease diagnosis, typing and staging.

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Section: Resultssupporting

confidence: 94%

Diagnosing, Typing, and Staging of Renal Cell Carcinoma by Designer Matrix-Based Urinary Metabolic Analysis

Wang

Chen

et al. 2022

Anal. Chem.

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“…Regulators and substrates of His phosphorylation have been previously linked to roles in tumorigenesis (ACLY(Carrer et al, 2019; Shah et al, 2016), LHPP(Hou et al, 2020; Li et al, 2019; Sun et al, 2020; Wang et al, 2021; F. Wu et al, 2020; Zhang et al, 2020; Zheng et al, 2018), PGAM5(Cheng et al, 2018; Ng Kee Kwong et al, 2018)), and metastasis (ACLY(Wen et al, 2019), PHPT1(Xu et al, 2010), PGAM5(Kang et al, 2015), NME1(Kantor et al, 1993; Khan et al, 2019; Lee et al, 2018; Steeg et al, 1988; Suzuki et al, 2004)) and localize to varying subcellular regions, based upon data from this study and previous publications (detailed in Table 1). Analyzing these proteins and pHis signals in mouse pancreatic tumors, we found that pHis signals were decreased as compared to normal pancreatic tissue and non-tumor or stromal cells.…”

Section: Discussionmentioning

confidence: 99%

Illuminating histidine phosphorylation in the pancreatic tumor microenvironment

Hunter

Wahl

Lytle

et al. 2022

Preprint

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Development of phosphohistidine (pHis) antibodies has significantly advanced our understanding of pHis contributions to tumor biology, including a tumor suppressive role for a pHis phosphatase, a metastasis suppressive role for His kinases, and pHis regulation of T cell receptor signaling. Using these antibodies, we investigated pHis pathway regulation in the mouse pancreatic tumor microenvironment. We identified deregulated expression of pHis and pHis phosphatases that correlated with mouse pancreatic tumor progression. We developed a protocol to circumvent the acid and heat-sensitivity of pHis signals, enabling their co-staining with other proteins in FFPE tissue, identifying a significant enrichment of 1-pHis and a subtype of 3-pHis signals (Gly-3-pHis) in the stroma. We discovered increased Gly-3-pHis levels in tumor-associated myeloid cells mainly resulting from elevated ATP citrate lyase 3-pHis levels and predicted the existence of pHis in cell-cell adhesion proteins.We provide evidence that mitochondrial delocalization of PGAM5, a pHis phosphatase with increased expression during pancreatic tumorigenesis, occurs in tumor cells as compared to stromal cells stromal cells, enabling access to PGAM5s known cytoplasmic substrate, pHis-NME (Non-MEtastatic), and two potential Gly-3pHis substrates, SCSα (Succinyl CoA Synthetase) and β-catenin. Overall, we introduce a new method and possible targets for future studies of pHis pathway deregulation during tumorigenesis.

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“…LHPP is closely associated with protein homodimerization and inorganic diphosphatase activity [ 5 , 6 , 8 ]. Recently, an increasing number of publications have suggested that LHPP serves as a tumor suppressor in different tumor types, such as hepatocellular carcinoma (HCC) [ 5 , 27 ], intrahepatic cholangiocarcinoma (ICC) [ 11 ], glioblastoma [ 28 ], melanoma [ 29 ], cervical [ 14 ], bladder [ 10 ], thyroid [ 30 ], pancreatic [ 12 ], renal [ 13 ] and colorectal cancers [ 15 , 16 ]. A reduction in LHPP expression is highly correlated with poor prognosis in patients with malignant diseases.…”

Section: Discussionmentioning

confidence: 99%

Does the LHPP gene share a common biological function in pancancer progression?

et al. 2022

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Although emerging evidence has revealed that LHPP, a histidine phosphatase protein, suppresses the progression of different cancers, a pan-cancer analysis still remains unavailable. Therefore, we first utilized different bioinformatics tools to explore the tumor inhibitory role of LHPP protein across 33 tumor types based on the TCGA project. Additionally, HGC-27 gastric cancer cells were used to evaluate the biological functions of LHPP after stable transfection with lentiviruses. Consequently, LHPP mRNA and protein expression were down-regulated in the most cancer tissues corresponding to normal tissues. The data showed that patients with higher LHPP performance had a better prognosis of overall survival (OS) and disease-free survival (DFS) in brain glioma and renal carcinoma. In addition, we found that enhancement of LHPP expression attenuated the proliferation, migration and invasion of gastric cancer cells. The expression levels of cell-cycle-related and EMT-related molecules, such as CDK4, CyclinD1, Vimentin and Snail, were clearly reduced. Moreover, a genetic alteration analysis showed that the most frequent mutation types in LHPP protein was amplification. The patients without LHPP mutation showed a better tendency of prognosis in UCEC, STAD and COAD. Cancer-associated fibroblast infiltration was also observed in head and neck squamous cell carcinoma, stomach adenocarcinoma and testicular germ cell tumors. In summary, our pancancer analysis among various tumor types could provide a comprehensive understanding of LHPP biological function in the progression of malignant diseases and promote the development of novel therapeutic targets.

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LHPP Inhibits the Proliferation and Metastasis of Renal Cell Carcinoma

Cited by 20 publications

References 14 publications

Diagnosing, Typing, and Staging of Renal Cell Carcinoma by Designer Matrix-Based Urinary Metabolic Analysis

Diagnosing, Typing, and Staging of Renal Cell Carcinoma by Designer Matrix-Based Urinary Metabolic Analysis

Illuminating histidine phosphorylation in the pancreatic tumor microenvironment

Does the LHPP gene share a common biological function in pancancer progression?

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