Last update 01 Nov 2024

MTHFD1L

Last update 01 Nov 2024

Basic Info

Synonyms

DKFZP586G1517, FLJ21145, Formyltetrahydrofolate synthetase

+ [4]

Introduction

May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism complementing thus the enzymatic activities of MTHFD2.

Drugs associated with MTHFD1L

MTHFD1 inhibitor(One-carbon therapeutics)

Target

MTHFD1L

Mechanism

MTHFD1L inhibitors

Active Org.

One-Carbon Therapeutics AB

Originator Org.

One-Carbon Therapeutics AB

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TH-9619

Target

MTHFD1L x MTHFD2

Mechanism

MTHFD1L inhibitors [+1]

Active Org.

The University of Sheffield [+1]

Originator Org.

The University of Sheffield [+1]

Active Indication

B-Cell Malignant Neoplasm [+2]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MTHFD1L

100 Translational Medicine associated with MTHFD1L

0 Patents (Medical) associated with MTHFD1L

169

Literatures (Medical) associated with MTHFD1L

01 Nov 2024·Molecular and Cellular Biochemistry

Hypoxia-induced SHMT2 protein lactylation facilitates glycolysis and stemness of esophageal cancer cells

Article

Author: Li, Yu ; Liu, Shiyuan ; Cheng, Yao ; Qiao, Zhe ; Li, Shaomin

Esophageal cancer (EC) is a familiar digestive tract tumor with highly lethal. The hypoxic environment has been demonstrated to be a significant factor in modulating malignant tumor progression and is strongly associated with the abnormal energy metabolism of tumor cells. Serine hydroxymethyl transferase 2 (SHMT2) is one of the most frequently expressed metabolic enzymes in human malignancies. The study was designed to investigate the biological functions and regulation mechanisms of SHMT2 in EC under hypoxia. We conducted RT-qPCR to assess SHMT2 levels in EC tissues and cells (TE-1 and EC109). EC cells were incubated under normoxia and hypoxia, respectively, and altered SHMT2 expression was evaluated through RT-qPCR, western blot, and immunofluorescence. The biological functions of SHMT2 on EC cells were monitored by performing CCK-8, EdU, transwell, sphere formation, glucose uptake, and lactate production assays. The SHMT2 protein lactylation was measured by immunoprecipitation and western blot. In addition, SHMT2-interacting proteins were analyzed by bioinformatics and validated by rescue experiments. SHMT2 was notably upregulated in EC tissues and cells. Hypoxia elevated SHMT2 protein expression, augmenting EC cell proliferation, migration, invasion, stemness, and glycolysis. In addition, hypoxia triggered lactylation of the SHMT2 protein and enhanced its stability. SHMT2 knockdown impeded the malignant phenotype of EC cells. Further mechanistic studies disclosed that SHMT2 is involved in EC progression by interacting with MTHFD1L. Hypoxia-induced SHMT2 protein lactylation and upregulated its protein level, which in turn enhanced MTHFD1L expression and accelerated the malignant progression of EC cells.

15 May 2024·Development

Optical coherence tomography-guided Brillouin microscopy highlights regional tissue stiffness differences during anterior neural tube closure in the Mthfd1l murine mutant

Article

Author: Singh, Manmohan ; Larin, Kirill V ; Aglyamov, Salavat R ; Scarcelli, Giuliano ; Ambekar, Yogeshwari S ; Finnell, Richard H ; Steele, John W ; Caiaffa, Carlo Donato ; Schill, Alexander W ; Wlodarczyk, Bogdan J ; Zhang, Jitao

ABSTRACTNeurulation is a highly synchronized biomechanical process leading to the formation of the brain and spinal cord, and its failure leads to neural tube defects (NTDs). Although we are rapidly learning the genetic mechanisms underlying NTDs, the biomechanical aspects are largely unknown. To understand the correlation between NTDs and tissue stiffness during neural tube closure (NTC), we imaged an NTD murine model using optical coherence tomography (OCT), Brillouin microscopy and confocal fluorescence microscopy. Here, we associate structural information from OCT with local stiffness from the Brillouin signal of embryos undergoing neurulation. The stiffness of neuroepithelial tissues in Mthfd1l null embryos was significantly lower than that of wild-type embryos. Additionally, exogenous formate supplementation improved tissue stiffness and gross embryonic morphology in nullizygous and heterozygous embryos. Our results demonstrate the significance of proper tissue stiffness in normal NTC and pave the way for future studies on the mechanobiology of normal and abnormal embryonic development.

01 Feb 2024·Current Cancer Drug Targets

Expression, Prognostic Value, and Immune Infiltration of MTHFD Family in Bladder Cancer

Article

Author: Ge, Cheng Guo ; Zhang, Jun Yong ; Wang, Shun De ; Zheng, Bai Shu

Background:The Methylenetetrahydrofolate Dehydrogenase (MTHFD) family plays an important role in the development and prognosis of a variety of tumors; however, the role of the MTHFD family in bladder cancer is unclear.Methods:R software, cBioPortal, GeneMANIA, and online sites such as String-LinkedOmics were used for bioinformatics analysis.Results:MTHFD1/1L/2 was significantly upregulated in bladder cancer tissues compared with normal tissues, high expression of the MTHFD family was strongly associated with poorer clinical grading and staging, and bladder cancer patients with upregulated expression of MTHFD1L/2 had a significantly worse prognosis. Gene function and PPI network analysis revealed that the MTHFD family and related genes play synergistic roles in the development of bladder cancer. 800 co-expressed genes related to the MTHFD family were used for functional enrichment analysis, and the results showed that many genes were associated with various oncogenic pathways such as cell cycle and DNA replication. More importantly, the MTHFD family was closely associated with multiple infiltrating immune lymphocytes, including Treg cells, and immune molecules such as TNFSF9, CD274, and PDCD1.Conclusion:Our study shows that MTHFD family genes may be potential prognostic markers and therapeutic targets for patients with bladder cancer.

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MTHFD1L

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