• ATF4 and SLC1A5 are upregulated in colorectal cancer tissues and positively correlate with TNM stages.
• ATF4 overexpression enhances colorectal cancer cell viability, migration, and invasion, while knockdown suppresses these phenotypes.
• SLC1A5 knockdown inhibits glutamine and glucose metabolism, reducing expression of glycolytic enzymes HK2 and PKM2.
• ATF4 directly binds to the SLC1A5 promoter, transcriptionally inducing SLC1A5 expression, thereby promoting glutaminolysis and glycolysis.