Table 1.

External/Applied/Mechanic Forces in GBM.

	Author	Stress Marker	Study Design	Effect on GBM
Stiffness	Chen et al. [6]	Piezo/PIEZO1	Drosophilia glioma model in vivo; mice xenograft experiments; RNA sequencing of two human GBM stem cell lines (G508 and G532)	Regulator of mitosis and tissue stiffness through activation of integrin-FAK signaling; correlated with GBM aggressiveness and decreased survival
	Miroshnikova et al. [7]	Tenascin C	Patient-derived samples; mouse model	ECM stiffness represses miR-203 expression which activates HIF1α-dependent TNC deposition, which may induce aggressiveness and lead to recurrence
	Sen et al. [8]	Talin-1	U373 MG human glioma cells	Involved in mechanical rigidity sensing; transmits signals from the ECM to the cytoskeleton through interplay of integrins and actin
	Khan et al. [9]	N/A	CD 133+ GBM cells	Actively migrating GBMs exhibit higher elastic stiffness at the front end, facilitating traction needed for forward movement through an anchoring effect
Tensile Force	Barnes et al. [10]	Tension (tenescin)	Patient-derived samples; mouse model	Tension-mediated glycocalyx–integrin feedback loop which promotes mesenchymal characteritistics
	Shen et al. [2]	Yes-associated protein (YAP)	G55 GBM cells	Re-localization of YAP to the cell nucleus indicates a higher degree of cytoskeletal tension during migration of GBM cells in a physically confined environment
Traction	de Semir et al. [11]	Pleckstrin homology domain-interacting protein (PHIP)	In vitro and in vivo murine model of U-251 GBM cell lines	Plays a role in activating the actin cytoskeleton, focal adhesion dynamics, migration, and invasion
	Gordon et al. [12]	Latex beads displacement and cell line volumetric growth	In vitro using human U87MGmEGFR GBM cell line	Demonstrated that tumor cells will grow towards the path of least resistance through traction-mediated forces
Drag Force	Agosti et al. [13]	N/A	U87 GBM cell lines	During proliferation, GBM aggregation is enabled when the adhesive force between cells is of the same magnitude of the drag forces of cells as they expand
Compression	Voutouri et al. [14]	Vessel option	Mathematical model	Compression led to hypoxia and resultant angiogenesis
	Calhoun et al. [15]	miR548 family	LN229 and U251 GBM cell lines; pathway analysis	Increased migration and decreased proliferation, characteristics associated with tumor aggressiveness
	Demou et al. [16]	Caveolin-1, integrin-β1, Rac1	U87 and HGL21 GBM cells	Cell deformation/compression leads to downregulation of E-cadherin (CDH1) and PECAM-1 (CD31) and overexpression of PTEN and Rac1; resultant decrease in cell adhesion and increased migration
Adhesion	Morjen et al. [17]	Kunitz-typeprotease inhibitor (PIVL)	In vitro using U87 cell lines; in vivo mouse model	Disrupted GBM migration, invasion, and adhesion through inhibition of integrin
	Yao et al. [18]	P311/PTZ17	In vivo mouse model	Rho GTPase-mediated promotion of migration of epidermal stem cells
Hydrostatic Pressure	Claus et al. [19]	N/A	Case report	Increased CSF protein concentration caused increased ICP and patient deterioration
	Takara et al. [20]	N/A	Case report	Increased CSF protein concentration led to hydrostatic pressure build up
	Zoi et al.	Polycystin-1 (PC1)	T98G GBM cells subjected to coninuous hydrostatic pressure and/or PC1 blockade	Hydrostatic pressure inhibited proliferation and migration of GBM cells. PC1 had the opposite effect
Magnetic Force	Perez et al. [21]	N/A	(U87) tumor spheroid aggregation methodology based on magnetic cell labeling; spheroid cell invasion w/ Matrigel	Magnetic properties of the spheroids allow for determination of surface tension
	Chen et al. [22]	Hexagonal superparamagnetic cones	U-343 GBM cell lines	Magnetic field gradient decreased cell growth and migration
Osmotic Pressure	Catacuzzeno et al. [23]	Swelling-activated chloride currents	In vitro using GL-15 GBM cells	Channel activation included shape and volume changes, allowing migration and invasion
	Pu et al. [24]	Caveolin-1, CAVIN1; uPA and MMPs; AQP1	U87, U118, and U251 GBM cell lines	Play a role in the response to increased pressure and GBM invasion
	Pu et al. [25]	Snail-1, Snail-2, N-cadherin, Twist, and vimentin	GBM cell lines U87 and U251; patient-derived neural oncospheres	EMT and invasion through production of matrix proteases as a response to osmotic/hydrostatic pressure
Shear Stress	Rezk et al. [26]	Nestin and vimentin; actin filaments, vinculin, paxillin, and FAK	Patient-derived samples	Increased migration and proliferation
Solid Stress	Ciarletta et al. [27]	N/A	Theoretical calculation of buckling instability from solid stresses	Residual stresses promote buckling instability and promote tumor invasion
	Stylianopoulos et al. [28]	Collagen, hyaluronan	Mathematical model	Increased perfusion of tumors led to improved oxygenation and drug delivery

N/A: Not applicable.