PTS is activated by ATF4 and promotes lung adenocarcinoma development via the Wnt pathway

Abstract

Background: The effects and mechanism of 6-pyruvoyl-tetrahydropterin synthase (PTS) on lung adenocarcinoma (LUAD) were studied in LUAD cells and mice with subcutaneously transplanted tumors. Methods: PTS level in tissues and cells was tested by immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). The impacts of PTS on cell viability, proliferation, apoptosis, invasion, and migration were determined by Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry, transwell assay, and wound healing assay, respectively. The Cancer Genome Atlas (TCGA) analysis and dual luciferase assay were conducted to predict and verify the relationship between PTS and activating transcription factor 4 (ATF4). A mouse model was established by subcutaneous injection with cancer cells. Tumor volume was calculated as V = ab 2 /2. Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to measure cell proliferation and apoptosis in tumors.Results: PTS was highly expressed in LUAD. Higher PTS level was correlated with late clinical stages and poor survival of patients. Down-regulation of PTS inhibited the viability and proliferation and induced apoptosis of LUAD cells. PTS was activated by ATF4, and up-regulation of ATF4 reversed the inhibitory effect of PTS silencing on LUAD cells. Silencing of PTS inhibited the Wnt pathway. Down-regulation of PTS inhibited tumor growth in mice.Conclusions: PTS was highly expressed in LUAD. PTS was activated by ATF4 and promoted LUAD development via the Wnt pathway.

Temporin-GHaK Exhibits Antineoplastic Activity against Human Lung Adenocarcinoma by Inhibiting the Wnt Signaling Pathway through miRNA-4516

“…The Wnt signaling pathway plays an important role in the development of LUAD [ 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. The phosphorylation of GSK-3β was a critical step in the activation of the Wnt signaling pathway [ 32 , 33 ].…”

Modulation of GCN2/eIF2α/ATF4 Pathway in the Liver and Induction of FGF21 in Young Goats Fed a Protein- and/or Phosphorus-Reduced Diet

“…Our results indicate that Phe is one of the EAA that is increased under dietary protein restriction, which could explain the increase in Tyr. Additionally, the 6-pyruvoyl-tetrahydropterin synthase (PTS) gene is activated by ATF4 and is as an important cofactor for hepatic PAH involved in the Phe-Tyr-pathway [ 46 ]. Finally, in the case of Pro, intracellular Pro concentrations have been shown to increase in response to ATF4 [ 47 , 48 , 49 ].…”

Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer

“…GOLPH3 interacts with CKAP4 and increases the secretion of exosomal WNT3A, leading to a cancer stem cell (CSC)-like phenotype and metastasis in NSCLC [ 54 ]. WNT5A expression was found to be upregulated by PTS [ 57 ], circVAPA [ 58 ], E2F1 [ 59 ] and ATF4 [ 60 ] (Table 2 ). Higher PTS level was found in LUAD and correlated with late clinical stages and poor survival [ 57 ].…”

“…WNT5A expression was found to be upregulated by PTS [ 57 ], circVAPA [ 58 ], E2F1 [ 59 ] and ATF4 [ 60 ] (Table 2 ). Higher PTS level was found in LUAD and correlated with late clinical stages and poor survival [ 57 ]. circVAPA acted as a ceRNA to up-regulate WNT5A by sponging miR-876-5p and thus activating Wnt/β-catenin signaling [ 58 ].…”