Alcohol consumption promotes colorectal carcinoma metastasis via a CCL5-induced and AMPK-pathway-mediated activation of autophagy
Authors: Mei Xu
Danlei Chen
Siying Wang
Yakun Liu
Shiqing Wang
Dandan Yu
Yu Jiang
Haodong Zhao
Rui Cao
Jia Luo
Journal: Scientific Reports (2018)
Discipline: Multidisciplinary
Keywords: alcohol consumption; colorectal cancer; progression; prognosis; tumor-node-metastasis (TNM)
Affiliations: Department of Pathophysiology, School of Basic Medicine, Anhui Medical University, Hefei, 230032, China., Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA., Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA. ., Department of Pathophysiology, School of Basic Medicine, Anhui Medical University, Hefei, 230032, China. .

Abstract:  There is a definite relationship between alcohol consumption and colorectal cancer (CRC) development. We investigated effect of alcohol consumption on CRC patients' progression and prognosis by utilizing epidemiological data and found patients with alcohol consumption increased risks of tumor-node-metastasis (TNM), organ metastasis and poorer prognosis. Because their tumor tissues displayed increased expression of C-C chemokine ligand 5 (CCL5), we hypothesized CCL5 might participate in cancer progression in such patients. Ethanol increased the secretion of CCL5 in two CRC cell lines, HT29 and DLD-1. Treatment with CCL5 directly increased migratory ability of these cells, whereas neutralization or knockdown of CCL5 can partially block alcohol-stimulated migration. We further investigated underlying mechanism of CCL5-induced migration. Our results indicated that effects of CCL5 on migration are mediated by the ability of CCL5 to induce autophagy, a cellular process known to be critical for migration. Using high-throughput sequencing and western blotting, we found induction of autophagy by CCL5 takes place via AMPK pathway. Aforementioned ethanol increases CCL5 secretion, CCL5 activates autophagy through AMPK pathway, and autophagy increases migration was confirmed by experiments with autophagy or AMPK inhibitors. To sum up, our study demonstrates that chronic alcohol consumption may promote metastasis of CRC through CCL5-induced autophagy. 

Retracted: No

PubPeer comments:
 This paper is part of a set of papers from the Aix-Marseille Universitu00e9 Institut Hospitalo-Universitaire Mu00e9diterranu00e9e-Infection in Marseille, France, that all describe novel microbial strains isolated from subjects in African and South American countries, but without mentioning ethical approval by local authorities, and without local authors. In this paper, a novel archaeal species is described, isolated from the stool of an obese 22y old Amazonian woman. The article offers few details, so I hope the authors could answer some questions here. * What was the approximate place of residence of the subject? Where in the Amazon? * Are there any details known about e.g. diet, living conditions (rural vs urban, agricultural vs. hunter gatherer) of the study subject? There is only limited value to describe a novel human-associated microbial species if those details about the human host are not given. * Although the stool sample was obtained from an Amazonian woman, the strain was named after Marseille, where the strain was discovered. That seems a bit researcher-centered. Why not name it after the residence of the woman? * How did the authors manage to transport this stool sample from the Amazon to the laboratory in France? Some details appear to be missing. Was the stool sample transported from Brazil back to France at some cold temperature, and then added to the blood culture bottle, or was the sample processed locally? Did local researchers or authorities participate? * The study mentions *the agreements of the National Ethics Committee of the IFR48 (Marseille, France) were obtained under number 09-022.* But that is a committee in France, not in Brazil. There is no word about obtaining IRB approval e.g. on consent wording with the local authorities. In addition, both authors are affiliated with institutions in France, without any local researchers to contribute. Could the authors please explain how the research was being performed, and why local researchers were not given a chance to participate? How was this individual selected? ,