Weight loss and cachexia are common problems in colorectal cancer patients;thus,parenteral and enteral nutrition support play important roles in cancer care.However,the impact of nonessential amino acid components of ...Weight loss and cachexia are common problems in colorectal cancer patients;thus,parenteral and enteral nutrition support play important roles in cancer care.However,the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied.In this study,we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival(P<0.001)than those who did not.Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice,predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis,resulting in mTORCl activation.mTORCl inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation.In addition,cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione.We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin.These findings indicate that cyst(e)ine;as part of supplemental nutrition,plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.展开更多
基金supported by National Key Research and Development Program of China[2020YFA0112300 and 2018YFC2000400 to C.C.]the National Natural Science Foundation of China[82072622,81860488,and 81560432 to Y.R.,81830087 and 31771516 to C.C.,81772847 to L.R.,81672639 to Z.Z.,and 81872414 and 81802671 to J.D.]+1 种基金Yunnan Leading Medical Talents Program[L-201610]to Y.R.,Yunnan Fundamental Research Projects[2019FB112]Yunnan excellent young scientist foundation(2020)to J.D.,and Project of Innovative Research Team of Yunnan Province[2018HC004 and 2019HC005].S.-C.J.Y.
文摘Weight loss and cachexia are common problems in colorectal cancer patients;thus,parenteral and enteral nutrition support play important roles in cancer care.However,the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied.In this study,we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival(P<0.001)than those who did not.Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice,predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis,resulting in mTORCl activation.mTORCl inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation.In addition,cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione.We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin.These findings indicate that cyst(e)ine;as part of supplemental nutrition,plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.
