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Several distinct metabolic alterations have been identified as key EMT phenotypes. In the present study, we further characterize the role of transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2)\u2010induced EMT in non\u2010small\u2010cell lung cancer. Our study revealed that TGF\u2010\u03b2 plays a role in EMT functions by upregulation of cytidine 5\u2032\u2010triphosphate synthetase 1 (CTPS), a vital enzyme for CTP biosynthesis in the pyrimidine metabolic pathway. Both knockdown and enzymatic inhibition of CTPS reduced TGF\u2010\u03b2\u2010induced changes in EMT marker expression, chemoresistance and migration <jats:italic>in\u2009vitro<\/jats:italic>. Moreover, <jats:italic>CTPS<\/jats:italic> knockdown counteracted the TGF\u2010\u03b2\u2010mediated downregulation of UDP\u2010glucuronate, glutarate, creatine, taurine and nicotinamide. 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