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Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in men and women in the United States. We have shown that tumors from female CRC patients have increased asparagine (Asn) which is positively associated with poorer overall survival for female patients only (n=196, stage I-III). Furthermore, analysis of asparagine synthetase (ASNS) expression shows that ASNS is similarly associated with poorer survival for females with CRC only. Currently it is not understood why there are sex-specific differences in tumor metabolism of Asn, or the roles of ASNS in CRC progression. Therefore, we hypothesize that limiting ASNS-driven Asn production is a viable target to suppress CRC development in a sex-specific manner. Therefore, we used a combination of in vitro and in vivo models with human CRC ASNS knock out (KO) cells to generate additional hypotheses that may reveal mechanisms that …