Cyst(e)ine in Nutrition Formulation Promotes Colon Cancer Growth and Chemoresistance by Activating MTORC1 and Scavenging ROS

Overview

Journal Signal Transduct Target Ther

Specialties Cell Biology
Pharmacology

Date 2021 May 28

PMID 34045438

Citations 22

Authors

Jiao Wu

Sai-Ching Jim Yeung

Sicheng Liu

Aiham Qdaisat

Dewei Jiang

Wenli Liu

Zhuo Cheng

Wenjing Liu

Haixia Wang

Lu Li

Zhongmei Zhou

Rong Liu

Chuanyu Yang

Ceshi Chen

Runxiang Yang

Affiliations

Soon will be listed here.

Abstract

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.

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