Recent advances of the mammalian target of rapamycin signaling in mesenchymal stem cells

Abstract

Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in a variety of cellular functions, such as cell proliferation, metabolism, autophagy, survival and cytoskeletal organization. Furthermore, mTOR is made up of three multisubunit complexes, mTOR complex 1, mTOR complex 2, and putative mTOR complex 3. In recent years, increasing evidence has suggested that mTOR plays important roles in the differentiation and immune responses of mesenchymal stem cells (MSCs). In addition, mTOR is a vital regulator of pivotal cellular and physiological functions, such as cell metabolism, survival and ageing, where it has emerged as a novel therapeutic target for ageing-related diseases. Therefore, the mTOR signaling may develop a large impact on the treatment of ageing-related diseases with MSCs. In this review, we discuss prospects for future research in this field.

Vascular smooth muscle cells in intimal hyperplasia, an update

“…Of note, inflammation and the NF-κB signaling pathway have also been reported to drive osteogenic VSMCs differentiation in various models ( Zhao et al, 2012 ; Zhou et al, 2014 ; Yoshida et al, 2017 ; Voelkl et al, 2018 ; Lee et al, 2019 ; Voelkl et al, 2019 ). In recent years, increasing evidence also suggest that mTOR plays important roles in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts and chondrocytes ( Cai et al, 2022 ). Thus, it is likely that mTOR pathways contribute to the formation VSMC-derived MSC and subsequent formation of myofibroblasts and osteo-chondrogenic-like VSMCs in the context of IH.…”

Target enzymes in serine‐glycine‐one‐carbon metabolic pathway for cancer therapy

“…SOX7 can bind to the MTHFD2 promoter and inhibit MTHFD2 expression, promoting SOX7‐mediated tumor suppression 133 . Moreover, mTORC1 can activate ATF4 and upregulate MTHFD2 expression by increasing formate production, which in turn increases de novo purine nucleotide synthesis in response to growth signals 134,135 . In Ewing sarcoma (EWS), the chimeric transcription factor EWS‐FLI1 is the major oncogenic driver, which positively regulates the expression of the glutamine transporter SLC1A5 and two enzymes involved in the one‐carbon cycle—MTHFD2 and MTHFD2L—and thus affects the cellular redox state 136 .…”

“…133 Moreover, mTORC1 can activate ATF4 and upregulate MTHFD2 expression by increasing formate production, which in turn increases de novo purine nucleotide synthesis in response to growth signals. 134,135 In Ewing sarcoma (EWS), the chimeric transcription factor EWS-FLI1 is the major oncogenic driver, which positively regulates the expression of the glutamine transporter SLC1A5 and two enzymes involved in the one-carbon cycle-MTHFD2 and MTHFD2L-and thus affects the cellular redox state. 136 In colorectal cancer, MTHFD2 is transcriptionally upregulated by MYC via KRAS proto-oncogenes (KRAS) downstream, including the PI3K/AKT and mitogen-activated protein kinase 1 (MAPK1) pathways, confers redox homeostasis and promotes cancer cell growth and metastasis.…”