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

Table 1 List of experimental studies investigating the effect of external pressure on colon cancer cells proliferation

Ref.	Applied load	Pressure loading system and experimental conditions	Results
Hirokawa et al[44], 1997	40-120 mmHg (5-16 kPa)	The pressure-loading apparatus consists of a flask of which cap was pierced and connected to a tubing by which compressed He gas was introduced to raise internal pressure.	Pressurization from 40 to 120 mmHg for 48 h significantly increased cell (IEC18) number with peak proliferation at 80 mmHg. Pressure-induced DNA synthesis was further enhanced by the addition of interleukin-2, suggesting the regulation of intestinal epithelial growth by pressure could be dependent on cytokines.
Hirokawa et al[43], 2001			Applied pressure for 48 h induced proliferation of IEC18 cell, with a significantly peak at 80 mmHg. The pattern of F-actin distribution was not significantly altered. The pressure-induced increase in phosphorylation of Elk-1 fusion protein corresponding to the activation of MAPK.
Basson et al[63], 2000	15 mmHg (2 kPa)	Cell plates was positioned in an airtight acrylic box, in which pressurized gas was introduced by a tubing to increase pressure.	Increasing ambient pressure stimulated the adhesion of human Caco-2, SW1116, SW620, and HT-29 cells to Matrigel, type I collagen, laminin, and fibronectin.
Whitehead et al[6], 2008	0.8 kPa	A controlled mechanical strain was applied on short segments of colon explants obtained from normal and APC1638N/+ mice. Tissues were placed into a mechanical deformation box and compressed in the z-direction of approximately half of their relaxed thickness for 20 min.	APC1638N/+ mice showed the expression of the two oncogenes Myc and Twist1, not observed in wild-type colon explants. Myc and Twist1 activation was found to be correlated with an increased presence of nuclear β-catenin . Almost no nuclear β-catenin was detected in the wild-type colon epithelium.
			The mechanical stimulation of APC1638N/+ tissue leads to the phosphorylation of β-catenin at tyrosine 654, the site of interaction with E-cadherin, affecting cell adhesions properties.
Fernández-Sánchez et al[5], 2015	1.2 kPa	A controlled pressure was applied in vivo in APC1638N/+ and control mice by subcutaneously inserting a magnet close to the mouse colon. The magnet generates a magnetic force on ultra-magnetic liposomes, stabilized in the mesenchymal cells of the connective tissue surrounding colonic crypts.	The magnetically induced load led to a rapid Ret activation and the phosphorylation of β-catenin on Tyr654, impairing its interaction with E-cadherin.
			β-catenin nuclear translocation was observed after 15 days with a consequent increased expression of β-catenin-target genes at 1 month, together with crypt enlargement accompanying the formation of early tumorous aberrant crypt foci.
			Such malignant behavior was induced in, both, APC1638N/+ and control mice, irrespective of the presence of prior genetic abnormalities.
Avvisato et al[27], 2007	1.5 kPa	Cells were plated on 38 mm × 76 mm slides and subjected to a laminar shear stress in a rectangular flow channel for 12 h.	β-catenin signalling of SW480 cells decreased to 22% of control values. The β-catenin signalling were measured for 0-24 h during shear stress exposure, it decreased significantly following 12 h of flow, reaching a minimum after 24 h.