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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2021; 13(11): 1632-1647
Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1632
Role of mammalian target of rapamycin complex 2 in primary and secondary liver cancer
Katharina Joechle, Jessica Guenzle, Claus Hellerbrand, Pavel Strnad, Thorsten Cramer, Ulf Peter Neumann, Sven Arke Lang
Katharina Joechle, Thorsten Cramer, Ulf Peter Neumann, Sven Arke Lang, Department of General, Visceral and Transplantation Surgery, University Hospital Rheinisch-Westfälisch Technische Hochschule Aachen, Aachen 52074, Germany
Jessica Guenzle, Department of General and Visceral Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg 79106, Germany
Claus Hellerbrand, Institute of Biochemistry, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen 91054, Germany
Pavel Strnad, Department of Internal Medicine III, University Hospital Rheinisch-Westfälisch Technische Hochschule Aachen, Aachen 52074, Germany
Author contributions: Joechle K and Lang SA contributed to conception and design the article; Joechle K, Hellerbrand C and Strnad P contributed to acquisition of data, drafting the article; All authors contributed to critical revision for important content and approved the final manuscript.
Conflict-of-interest statement: The authors declare that they have no conflicting interests.
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: Sven Arke Lang, FEBS, MD, Professor, Senior Researcher, Surgeon, Department of General, Visceral and Transplantation Surgery, University Hospital Rheinisch-Westfälisch Technische Hochschule Aachen, Pauwelsstraße 30, Aachen 52074, Germany.svlang@ukaachen.de
Received: February 25, 2021
Peer-review started: February 25, 2021
First decision: April 19, 2021
Revised: April 30, 2021
Accepted: August 16, 2021
Article in press: August 16, 2021
Published online: November 15, 2021
Processing time: 259 Days and 18 Hours
Abstract

The mammalian target of rapamycin (mTOR) acts in two structurally and functionally distinct protein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Upon deregulation, activated mTOR signaling is associated with multiple processes involved in tumor growth and metastasis. Compared with mTORC1, much less is known about mTORC2 in cancer, mainly because of the unavailability of a selective inhibitor. However, existing data suggest that mTORC2 with its two distinct subunits Rictor and mSin1 might play a more important role than assumed so far. It is one of the key effectors of the PI3K/AKT/mTOR pathway and stimulates cell growth, cell survival, metabolism, and cytoskeletal organization. It is not only implicated in tumor progression, metastasis, and the tumor microenvironment but also in resistance to therapy. Rictor, the central subunit of mTORC2, was found to be upregulated in different kinds of cancers and is associated with advanced tumor stages and a bad prognosis. Moreover, AKT, the main downstream regulator of mTORC2/Rictor, is one of the most highly activated proteins in cancer. Primary and secondary liver cancer are major problems for current cancer therapy due to the lack of specific medical treatment, emphasizing the need for further therapeutic options. This review, therefore, summarizes the role of mTORC2/Rictor in cancer, with special focus on primary liver cancer but also on liver metastases.

Keywords: Mammalian target of rapamycin; Mammalian target of rapamycin complex 2; Rictor; Liver cancer; Liver metastases; Hepatocellular carcinoma; Cholangiocellular carcinoma

Core Tip: Mammalian target of rapamycin complex 2 (mTORC2) has recently gained importance in cancer research, as it is one of the key effectors of the PI3K/AKT/mTOR pathway and stimulates cell growth, cell survival, metabolism, and cytoskeletal organization. Rictor, the central subunit of mTORC2, was found to be upregulated in different kinds of cancers and is associated with a bad prognosis. We herein discuss the implications of mTORC2 in primary and secondary liver cancer.