Fig. 1
From: Cancer cells with trapped nuclei cut their way through the extracellular matrix
Nuclear constriction triggers delivery of vesicular MT1-MMP to the plasma membrane. a When cells invade through extracellular matrices (ECM) with large pores (pore size greater than the nucleus), there are few physical constraints on the nucleus and the centrosome–nucleus axis is not under tension resulting in a longer centrosome–nucleus distance. Low nuclear tension or little deformation are observed and the MT1-MMP delivery system is not triggered, as there is no need for collagenolysis to relieve physical constriction. b Cells invading into denser ECM, with pore size smaller than the nucleus, face a physical barrier to their movement. The matrix imposes a nuclear constriction [1] in the cell moving forward and creates nuclear tension that is sensed via the centrosome–nucleus linkage [2] which becomes stronger as evidenced by reduced centrosome–nucleus distance. This leads to the recruitment of intracellular MT1-MMP, stored in late endosomes, that then traffic to the site of physical constriction [3] on the plasma membrane. MT1-MMP then mediates ECM degradation to relieve the tension and make space for the nucleus to go through [4]. Integrins, also present in the same region of the plasma membrane, may then mediate uptake of the degraded matrix, in a tensin-dependent fashion. Degraded ECM then traffics to the late endosomes where it can support mTOR activation, a metabolic sensor [5]. Thus, focussed proteolysis at the points of nuclear constriction followed by ECM uptake through ligand-bound integrin internalisation may help cancer cells to scavenge nutrients to maintain energy balance
