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Integrated proteomics and phosphoproteomics analyses reveal the broad and complex influence by inhibition of L-type amino acid transporter-1 in biliary tract carcinoma cells

ABSTRACT: To characterize the changes of phosphorylation signaling cascades and protein expressions induced by LAT1 inhibition in 4 cell lines of biliary tract cancer treated with LAT1 specific inhibitor JPH203, immobilized metal affinity chromatography and liquid chromatography-tandem mass spectrometry with MS2-based quantitation of tandem mass tag were utilized.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Yoshikatsu Kanai

PROVIDER: PXD019458 | JPOST Repository | Fri Dec 25 00:00:00 GMT 2020

REPOSITORIES: jPOST

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			Action	DRS
	01_IMAC_HuCCT1_JPH_1d.mzTab	Mztab
	01_IMAC_HuCCT1_JPH_1d_01.raw	Raw
	01_IMAC_HuCCT1_JPH_1d_02.raw	Raw
	01_IMAC_HuCCT1_JPH_1d_03.raw	Raw
	01_IMAC_HuCCT1_JPH_1d_04.raw	Raw

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Publications

Proteomics and phosphoproteomics reveal key regulators associated with cytostatic effect of amino acid transporter LAT1 inhibitor.

Okanishi Hiroki H Ohgaki Ryuichi R Okuda Suguru S Endou Hitoshi H Kanai Yoshikatsu Y

Cancer science 20201219 2

L-type amino acid transporter 1 (LAT1) is highly expressed in various cancers and plays important roles not only in the amino acid uptake necessary for cancer growth but also in cellular signaling. Recent research studies have reported anticancer effects of LAT1 inhibitors and demonstrated their potential for cancer therapy. Here, we characterized the proteome and phosphoproteome in LAT1-inhibited cancer cells. We used JPH203, a selective LAT1 inhibitor, and performed tandem mass tag-based quant ...[more]

PMID: 33264461

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Inhibition of L-type amino acid transporter 1 induces disruption of cancer amino acid homeostasis with altered cellular signals

Project description:This study characterized the changes of phosphorylation signaling cascades induced by LAT1 inhibition in three cell lines of biliary tract cancer treated with LAT1 specific inhibitor JPH203 for 15 and 30 min. Immobilized metal affinity chromatography and liquid chromatography-tandem mass spectrometry with MS2-based quantitation of tandem mass tag were utilized.

2023-05-24 | PXD034276 | JPOST Repository

AKT signaling mediates the cellular adaptation to LAT1 pharmacologic inhibition in pancreatic ductal adenocarcinoma.

Project description:To characterize the changes of phosphorylation signaling cascades induced by LAT1 inhibition in MIA PaCa-2 cells treated with LAT1 specific inhibitor JPH203, immobilized metal affinity chromatography and liquid chromatography-tandem mass spectrometry with MS2-based quantitation of tandem mass tag were utilized. To characterize the changes of protein expressions induced by LAT1 inhibition and AKT inhibition in MIA PaCa-2 cells exposed to LAT1 specific inhibitor JPH203 with or without AKT inhibitor MK-2206, immobilized metal affinity chromatography and liquid chromatography-tandem mass spectrometry with MS2-based quantitation of tandem mass tag were utilized.

2024-04-15 | PXD034389 | JPOST Repository

mRNA expression profiling of ERCP biliary brushings of malignant biliary strictures

Project description:Identification of differential gene expression uging endoscopic biliary brushings Bile duct brishings of benign biliary strictures and malignant biliary strictures, samples snap frozen in liquid nitrogen

2012-03-01 | E-GEOD-34166 | biostudies-arrayexpress

Integration of Metabolomics and Transcriptomics Reveals HDL-Driven Biliary Reverse Cholesterol Transport Involved in the Antiatherogenic Effect of San-wei-tan-xiang Capsule

Project description:Biliary reverse cholesterol transport (RCT) plays a crucial role in cholesterol clearance and regulation of atherogenesis. San-wei-tan-xiang capsule (SWTX), a traditional Chinese medicine, has shown potential in inhibiting atherogenesis by increasing high-density lipoprotein (HDL) cholesterol levels and promoting macrophage-mediated cholesterol efflux. However, the specific role of HDL-driven cholesterol metabolism in the anti-atherogenic effects of SWTX remains unclear. In this study, liquid chromatography coupled with tandem mass spectrometry was used to analyze the circulating metabolic profile, and RNA sequencing was performed on liver samples from ApoE−/− mice fed a cholesterol-enriched diet. We found that SWTX treatment induced significantly differential expression of metabolites and genes involved in cholesterol and lipid metabolism, as well as bile secretion pathways, which are critical for HDL-driven biliary RCT. Furthermore, alterations in L-carnitine and choline metabolism induced by SWTX treatment was involved in the atheroprotective effects of SWTX. Notably, SWTX treatment led to a significant increase in the expression of cholesterol 7α-hydroxylase (CYP7A1), a key enzyme involved in bile acid synthesis during atherogenesis. Additionally, the expression of CYP7A1 and CYP7A1-mediated bile acid secretion were enhanced by the addition of choline in hepatic cells, suggesting that SWTX-induced elevation of choline metabolic products may contribute to the upregulation of CYP7A1 and CYP7A1-mediated biliary RCT. Overall, SWTX demonstrated its ability to attenuate atherosclerotic plaque formation, which can be attributed to alterations in carnitine and choline metabolism, as well as the modulation of CYP7A1-mediated HDL-driven biliary RCT.

2024-06-12 | GSE236672 | GEO

Primary Biliary Cirrhosis

Project description:Primary Biliary Cirrhosis

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Human biliary epithelial cells from discarded donor livers rescue bile duct structure and function in a mouse model of biliary disease

Project description:Biliary diseases can cause inflammation, fibrosis, bile duct destruction and eventually liver failure. There are no curative treatments for biliary disease except for liver transplantation. New therapies are urgently required. We have purified human Biliary Epithelial Cells (hBEC) from discarded human livers. hBECs were tested as a cell therapy in a mouse model of biliary disease where the conditional deletion of Mdm2 in cholangiocytes causes senescence, biliary strictures and fibrosis. hBEC are expandable, phenotypically stable and help restore biliary structure and function, highlighting their regenerative capacity and a potential alternative to liver transplantation for biliary disease.

2022-03-03 | GSE155498 | GEO

Biliary organoids uncover delayed epithelial development and barrier function in biliary atresia.

Project description:Background: RNASeq was performed on organoids derived from livers of normal healthy donors and patients with biliary atresia to characterize transcriptomic signatures. Methods: Organoids generated from livers of normal healthy donors and patients with biliary atresia were cultured either in expansion (undifferentiated: 3 NCOs and 11 BACOs) or differentiation medium (differentiated: 3 BACOs). Liver tissues obtained from deceased-donor subjects served as normal controls (N=3). Total RNA was isolated from organoids and liver biopsy tissue specimens. Results: Organoids from patients with biliary atresia showed abnormal cell polarity, loss of tight junctions, increased permeability and decreased expression of genes related to epidermal growth factor (EGF)- and fibroblast growth factor 2 (FGF2)-signaling. When treated with EGF+FGF2, biliary atresia organoids expressed differentiation and functional markers with restored cell polarity. Conclusion: Organoids from biliary atresia are viable and have evidence of halted epithelial development. The induction of developmental markers, improved cell‐cell junction, and decreased epithelial permeability by EGF and FGF2 identifies potential strategies to promote epithelial maturation and function.

2021-10-25 | GSE186444 | GEO

mRNA expression profiling of ERCP biliary brushings of malignant biliary strictures

Project description:Identification of differential gene expression uging endoscopic biliary brushings

2012-03-01 | GSE34166 | GEO

Bile proteome reveals biliary regeneration during normothermic preservation of human donor livers

Project description:Normothermic machine perfusion (NMP) after static cold storage is increasingly used for preservation and assessment of human donor livers prior to transplantation. Biliary viability assessment during NMP reduces the risk of post-transplant biliary complications. However, understanding molecular changes in the biliary system during NMP remains incomplete. Here, we performed RNA-seq analysis of donor livers undergoing NMP treatment and compared livers with biliary viability scores that were acceptable for transplantation vs those that were not.

2023-11-21 | E-MTAB-13501 | biostudies-arrayexpress

Transcriptional profiling of hepatocyte, reprogrammed hepatocyte, and biliary cells [human]

Project description:Comparison of transcripts between human hepatocytes, human hepatocytes reprogrammed into biliary cells, and human biliary cells shows similarities between reprogrammed cells and the untreated biliary population

2020-09-09 | GSE157661 | GEO

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