{Reference Type}: Journal Article
{Title}: The role of cytidine 5'-triphosphate synthetase 1 in metabolic rewiring during epithelial-to-mesenchymal transition in non-small-cell lung cancer.
{Author}: Nakasuka F;Hirayama A;Makinoshima H;Yano S;Soga T;Tabata S;
{Journal}: FEBS Open Bio
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 19
{Factor}: 2.792
{DOI}: 10.1002/2211-5463.13860
{Abstract}: Epithelial-to-mesenchymal transition (EMT) contributes to the poor prognosis of patients with cancer by promoting distant metastasis and anti-cancer drug resistance. Several distinct metabolic alterations have been identified as key EMT phenotypes. In the present study, we further characterize the role of transforming growth factor-β (TGF-β)-induced EMT in non-small-cell lung cancer. Our study revealed that TGF-β plays a role in EMT functions by upregulation of cytidine 5'-triphosphate synthetase 1 (CTPS), a vital enzyme for CTP biosynthesis in the pyrimidine metabolic pathway. Both knockdown and enzymatic inhibition of CTPS reduced TGF-β-induced changes in EMT marker expression, chemoresistance and migration in vitro. Moreover, CTPS knockdown counteracted the TGF-β-mediated downregulation of UDP-glucuronate, glutarate, creatine, taurine and nicotinamide. These findings indicate that CTPS plays a multifaceted role in EMT metabolism, which is crucial for the malignant transformation of cancer through EMT, and underline its potential as a promising therapeutic target for preventing drug resistance and metastasis in non-small-cell lung cancer.