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World J Hepatol. Aug 27, 2020; 12(8): 475-484
Published online Aug 27, 2020. doi: 10.4254/wjh.v12.i8.475
Cell competition in liver carcinogenesis
Fabio Marongiu, Ezio Laconi
Fabio Marongiu, Ezio Laconi, Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, Cagliari 09124, Italy
Author contributions: Marongiu F contributed to the planning and the writing of the MS and prepared the figures; Laconi E conceived the manuscript and contributed to its planning and writing.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ezio Laconi, MD, PhD, Academic Fellow, Associate Professor, Department of Biomedical Sciences, Unit of Experimental Medicine, University of Cagliari, Via Jenner, Cagliari 09124, Italy. elaconi@unica.it
Received: March 3, 2020
Peer-review started: March 3, 2020
First decision: April 2, 2020
Revised: June 22, 2020
Accepted: July 26, 2020
Article in press: July 26, 2020
Published online: August 27, 2020
Processing time: 175 Days and 1.7 Hours
Abstract

Cell competition is now a well-established quality control strategy to optimize cell and tissue fitness in multicellular organisms. While pursuing this goal, it is also effective in selecting against altered/defective cells with putative (pre)-neoplastic potential, thereby edging the risk of cancer development. The flip side of the coin is that the molecular machinery driving cell competition can also be co-opted by neoplastic cell populations to expand unchecked, outside the boundaries of tissue homeostatic control. This review will focus on information that begins to emerge regarding the role of cell competition in liver physiology and pathology. Liver repopulation by normal transplanted hepatocytes is an interesting field of investigation in this regard. The biological coordinates of this process share many features suggesting that cell competition is a driving force for the clearance of endogenous damaged hepatocytes by normal donor-derived cells, as previously proposed. Intriguing analogies between liver repopulation and carcinogenesis will be briefly discussed and the potential dual role of cell competition, as a barrier or a spur to neoplastic development, will be considered. Cell competition is in essence a cooperative strategy organized at tissue level. One facet of such cooperative attitude is expressed in the elimination of altered cells which may represent a threat to the organismal community. On the other hand, the society of cells can be disrupted by the emergence of selfish clones, exploiting the molecular bar codes of cell competition, thereby paving their way to uncontrolled growth.

Keywords: Cell competition; Liver carcinogenesis; Liver repopulation; Aging; Tissue homeostasis; Clonal expansion

Core tip: Cell competition stands as an eminently cooperative strategy which operates in coordination with mechanisms overlooking tissue mass and tissue architecture. One facet of such cooperative attitude is also expressed in the elimination of altered, putative (pre)-neoplastic cells which may potentially pose a threat to the organismal community. On the other hand, cell populations on the path towards neoplasia may cheat the society of cells from which they originate using the molecular bar codes of cell competition, thereby paving their way to uncontrolled growth, invasiveness and metastatic capacity.