Changes in cellular mechanical properties during onset or progression of colorectal cancer

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.