机构：[1]Department of the Second Medical Oncology, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China[2]Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA[3]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China[4]Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA[5]Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China[6]KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China[7]Institute of Translation Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China深圳市第二人民医院深圳医学信息中心
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 mTORC1 activation. mTORC1 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.
基金：
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.], Yunnan Leading Medical Talents Program [L-201610] to Y.R., Yunnan
Fundamental Research Projects [2019FB112] and 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. was a member of an expert panel for
Celgene, Inc. S.-C.J.Y. had funding support from Bristol-Myer Squibb, Inc. and
DepoMed, Inc. for investigator-initiated clinical studies.
第一作者机构：[1]Department of the Second Medical Oncology, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
共同第一作者：
通讯作者：
通讯机构：[3]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China[6]KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China[7]Institute of Translation Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
推荐引用方式(GB/T 7714)：
Wu Jiao,Yeung Sai-Ching Jim,Liu Sicheng,et al.Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS.[J].SIGNAL TRANSDUCTION AND TARGETED THERAPY.2021,6(1):doi:10.1038/s41392-021-00581-9.
APA：
Wu Jiao,Yeung Sai-Ching Jim,Liu Sicheng,Qdaisat Aiham,Jiang Dewei...&Yang Runxiang.(2021).Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS..SIGNAL TRANSDUCTION AND TARGETED THERAPY,6,(1)
MLA：
Wu Jiao,et al."Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS.".SIGNAL TRANSDUCTION AND TARGETED THERAPY 6..1(2021)
医学