Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS
| Autor: | Dewei Jiang, Wenli Liu, Aiham Qdaisat, Lu Li, Haixia Wang, Sai Ching J. Yeung, Wenjing Liu, Runxiang Yang, Rong Liu, Zhongmei Zhou, Ceshi Chen, Jiao Wu, Sicheng Liu, Chuanyu Yang, Zhuo Cheng |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Colorectal cancer QH301-705.5 Cystine Therapeutics Mechanistic Target of Rapamycin Complex 1 Article Cachexia 03 medical and health sciences chemistry.chemical_compound Gastrointestinal cancer 0302 clinical medicine Genetics medicine Humans Biology (General) business.industry Cancer medicine.disease HCT116 Cells Oxaliplatin Neoplasm Proteins Irinotecan 030104 developmental biology Parenteral nutrition chemistry Drug Resistance Neoplasm 030220 oncology & carcinogenesis Colonic Neoplasms Cancer research Medicine business Reactive Oxygen Species HT29 Cells medicine.drug |
| Zdroj: | Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-13 (2021) Signal Transduction and Targeted Therapy |
| ISSN: | 2059-3635 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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