MLXIPL promotes the migration, invasion, and glycolysis of hepatocellular carcinoma cells by phosphorylation of mTOR.

BMC Cancer

Department of General Surgery, The First Affiliated Hospital of Xi'an Medical University, No. 48, Fenghao West Road, Lianhu District, 710077, Xi'an, Shaanxi, China.

Published: February 2023

AI Article Synopsis

  • Hepatocellular carcinoma (HCC) has high incidence and mortality rates, and MLX interacting protein like (MLXIPL) is identified as a key regulator of metabolism involved in tumor growth.
  • The study used various methods, including qPCR and assays, to analyze the effects of MLXIPL on HCC cell behaviors and its interaction with mTOR.
  • Findings indicated that elevated MLXIPL levels in HCC promoted cancer cell growth and migration through activating mTOR phosphorylation, highlighting the significance of MLXIPL and mTOR in HCC progression.

Article Abstract

Background: Hepatocellular carcinoma (HCC) is associated with a high occurrence, mortality, and poor prognosis. MLX interacting protein like (MLXIPL) is an important regulator of glucolipid metabolism and is involved in tumor progression. We aimed to clarify the role of MLXIPL in HCC and its underlying mechanisms.

Methods: The level of MLXIPL was predicted using bioinformatic analysis and verified using quantitative real-time PCR (qPCR), immunohistochemical analysis, and western blot. We assessed the effects of MLXIPL on biological behaviors using the cell counting kit-8, colony formation, and Transwell assay. Glycolysis was evaluated using the Seahorse method. The interaction between MLXIPL and mechanistic target of rapamycin kinase (mTOR) was confirmed using RNA immunoprecipitation and co-immunoprecipitation. mTOR expression was detected in HCC cells using qPCR, immunofluorescence analysis, and western blot.

Results: The results showed that MLXIPL levels were elevated in both HCC tissues and HCC cell lines. Knockdown of MLXIPL impeded HCC cell growth, invasion, migration, and glycolysis. Moreover, MLXIPL combined with mTOR to induce phosphorylation of mTOR. Activated mTOR abrogated the effects on cellular processes induced by MLXIPL.

Conclusion: MLXIPL promoted the malignant progression of HCC by activating phosphorylation of mTOR, suggesting an important role of the combination of MLXIPL and mTOR in HCC.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9945719PMC
http://dx.doi.org/10.1186/s12885-023-10652-5DOI Listing

Publication Analysis

Top Keywords

phosphorylation mtor
12
mlxipl
11
hepatocellular carcinoma
8
mtor
8
hcc
8
analysis western
8
hcc cell
8
mlxipl promotes
4
promotes migration
4
migration invasion
4

Similar Publications

Bladder cancer (BC) is the tenth most common tumor worldwide, characterized by high incidence rates and mortality. This study aimed to explore the role of Methyltransferase like 13 (METTL13) in BC cells. J82 and T24 cells were cultured for experiments.

View Article and Find Full Text PDF

Zn inhibits PEDV replication by inducing autophagy through the Akt-mTOR pathway.

Vet Microbiol

December 2024

State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China. Electronic address:

Porcine epidemic diarrhea virus (PEDV) is a coronavirus that induces diarrhea in pigs, leading to severe economic losses in the global pig industry. Currently, effective antiviral treatments for porcine epidemic diarrhea (PED) are rarely available for clinical use. Zinc (Zn), an essential mineral, is known to reduce diarrhea in piglets transitioning from milk to solid feed by modulating immune system activity.

View Article and Find Full Text PDF

Inositol phosphates dynamically enhance stability, solubility and catalytic activity of mTOR.

J Biol Chem

December 2024

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, 37232; Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, 37232. Electronic address:

Mechanistic Target of Rapamycin (mTOR) binds the small metabolite inositol hexakisphosphate (IP) as shown in structures of mTOR, however it remains unclear if IP, or any other inositol phosphate species, function as an integral structural element(s) or catalytic regulator(s) of mTOR. Here, we show that multiple, exogenously added inositol phosphate species can enhance the ability of mTOR and mTORC1 to phosphorylate itself and peptide substrates in in vitro kinase reactions, with the higher order phosphorylated species being more potent (IP=IP>IP>>IP). IP increased the V and decreased the apparent K of mTOR for ATP.

View Article and Find Full Text PDF

Rap1 and mTOR signaling pathways drive opposing immunotoxic effects of structurally similar aryl-OPFRs, TPHP and TOCP.

Environ Int

December 2024

Guangdong Provincial Key Laboratory of Water Quality Improvement and Ecological Restoration for Watersheds, School of Ecology, Environment and Resources, Guangdong University of Technology, Guangzhou 510006, China; Guangdong Provincial Laboratory of Chemistry and Fine Chemical Engineering Jieyang Center, Jieyang 515200, China; School of Environmental and Chemical Engineering, Wuyi University, Jiangmen 529020, China.

Aryl organophosphorus flame retardants (aryl-OPFRs), commonly used product additives with close ties to daily life, have been regrettably characterized by multiple well-defined toxicity risks. Triphenyl phosphate (TPHP) and tri-o-cresyl phosphate (TOCP), two structurally similar aryl-OPFRs, were observed in our previous study to exhibit contrasting immunotoxic effects on THP-1 macrophages, yet the underlying mechanisms remain unclear. This study sought to address the knowledge gap by integrating transcriptomic and metabolomic analyses to elucidate the intricate mechanisms.

View Article and Find Full Text PDF

Through in vitro and in vivo experiments, combined with network pharmacology and molecular docking techniques, this study investigated the mechanism of action of osthole in the treatment of colorectal cancer(CRC). The relevant targets of osthole and CRC were retrieved from the SwissTargetPrediction and SuperPred in drug databases, as well as GeneCards and OMIM in disease databases. Protein-protein interaction(PPI) networks were constructed using the STRING database and Cytoscape 3.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: