Research progress on the relationship between the TOR signaling pathway regulator, epigenetics, and tumor development

Abstract

Almost all cellular activities depend on protein folding, signaling complex assembly/disassembly, and epigenetic regulation. One of the most important regulatory mechanisms responsible for controlling these cellular processes is dynamic protein phosphorylation/dephosphorylation. Alterations in phosphorylation networks have major consequences in the form of disorders, including cancer. Many signaling cascades, including the target of rapamycin (TOR) signaling, are important participants in the cell cycle, and dysregulation in their phosphorylation/dephosphorylation status has been linked to malignancies. As a TOR signaling regulator, protein phosphatase 2A (PP2A) is responsible for most of the phosphatase activities inside the cells. On the other hand, TOR signaling pathway regulator (TIPRL) is an essential PP2A inhibitory protein. Many other physiological roles have also been suggested for TIPRL, such as modulation of TOR pathways, apoptosis, and cell proliferation. It is also reported that TIPRL was increased in various carcinomas, including non-small-cell lung carcinoma (NSCLC) and hepatocellular carcinomas (HCC). Considering the function of PP2A as a tumor suppressor and also the effect of the TIPRL/PP2A axis on apoptosis and proliferation of cancer cells, this review aims to provide a complete view of the role of TIPRL in cancer development in addition to describing TIPRL/PP2A axis and its epigenetic regulation.

m6A-methylated KCTD21-AS1 regulates macrophage phagocytosis through CD47 and cell autophagy through TIPR

“…TIPRL, an essential PP2A inhibitory protein, plays an important role in cell apoptosis and cell proliferation. The protein is upregulated in various carcinomas, including NSCLC 21 . TIPRL affects cell growth and autophagy through light chain 3 (LC3)-II/I 22 .…”

“…TIPRL, an essential PP2A inhibitory protein, increases in various cancers, including NSCLC and hepatocellular carcinomas 21 . TIPRL plays important roles in cell apoptosis and proliferation of cancer through the TIPRL/PP2A axis.…”

The Pro-Oncogenic Sphingolipid-Metabolizing Enzyme β-Galactosylceramidase Modulates the Proteomic Landscape in BRAF(V600E)-Mutated Human Melanoma Cells

“…Finally, GALC-upregulated proteins include the TOR signaling pathway regulator, an allosteric regulator of the serine/threonine-protein phosphatase 2A in cancer cells [ 32 ], and the cytosolic X-prolyl aminopeptidase 1 associated with disease progression and shorter overall survival in multiple myeloma [ 33 ], together with 3′(2′), 5′-bisphosphate nucleotidase 2 and CXXC motif-containing zinc-binding protein, whose function(s) in cancer remains unexplored.…”

“…TOR signaling pathway regulator TIPRL Allosteric regulator of serine/threonine-protein phosphatase 2A. The TIPRL/PP2A axis affects apoptosis and proliferation of cancer cells [32].…”