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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2016; 22(32): 7203-7214
Published online Aug 28, 2016. doi: 10.3748/wjg.v22.i32.7203
Changes in cellular mechanical properties during onset or progression of colorectal cancer
Gabriele Ciasca, Massimiliano Papi, Eleonora Minelli, Valentina Palmieri, Marco De Spirito
Gabriele Ciasca, Massimiliano Papi, Eleonora Minelli, Valentina Palmieri, Marco De Spirito, Istituto di Fisica, Università Cattolica del Sacro Cuore, 00168 Roma, Italy
Author contributions: Papi M and De Spirito M designed research; Ciasca G, Minelli E, Papi M and Palmieri V wrote the paper; De Spirito M supervised the work; all authors discussed and commented on the manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Dr. Massimiliano Papi, Professor, Institute of Physics, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Roma, Italy. massimiliano.papi@unicatt.it
Telephone: +39-6-30154265 Fax: +39-6-3013858
Received: May 13, 2016
Peer-review started: May 16, 2016
First decision: June 20, 2016
Revised: July 11, 2016
Accepted: August 1, 2016
Article in press: August 1, 2016
Published online: August 28, 2016
Processing time: 103 Days and 8.1 Hours
Abstract

Colorectal cancer (CRC) development represents a multistep process starting with specific mutations that affect proto-oncogenes and tumour suppressor genes. These mutations confer a selective growth advantage to colonic epithelial cells that form first dysplastic crypts, and then malignant tumours and metastases. All these steps are accompanied by deep mechanical changes at the cellular and the tissue level. A growing consensus is emerging that such modifications are not merely a by-product of the malignant progression, but they could play a relevant role in the cancer onset and accelerate its progression. In this review, we focus on recent studies investigating the role of the biomechanical signals in the initiation and the development of CRC. We show that mechanical cues might contribute to early phases of the tumour initiation by controlling the Wnt pathway, one of most important regulators of cell proliferation in various systems. We highlight how physical stimuli may be involved in the differentiation of non-invasive cells into metastatic variants and how metastatic cells modify their mechanical properties, both stiffness and adhesion, to survive the mechanical stress associated with intravasation, circulation and extravasation. A deep comprehension of these mechanical modifications may help scientist to define novel molecular targets for the cure of CRC.

Keywords: Colorectal cancer; Biomechanics; Pressure; Mechanical signalling; Atomic force microscopy; Wnt

Core tip: Physical forces, either within tissues or externally applied, affect all tissues of the body. Cell mechanotransduction converts such forces into cellular responses that affect gene expression, protein synthesis, proliferation and morphogenesis. Here, we focused on recent studies covering the impact of physical stimuli such as compression, shear stress, adhesion and stiffness, in the development of colorectal cancer. We highlight that such stimuli play a major role in the tumor progression, affecting the Wnt pathway, being involved in the differentiation of non-invasive cells into metastatic variants and helping metastatic cells to survive the mechanical stress associated with intravasation, circulation and extravasation.