Fig. 1

Alterations in tumor matrix stiffness: normal organs are surrounded by irregularly thin collagen, which forms an ECM that is compliant and soft. In several solid tumors, the accumulation of ECM proteins causes a gradual rise in matrix stiffness parallel with the tumor’s growth. Tumor cells and other TME cells, particularly cancer-associated fibroblasts (CAF), produce collagen and Lysyl oxidase (LOX), resulting in collagen crosslinking, ECM rearrangement, and increased stiffness. In addition, increasing stiffness within tumors contributes to the continuous activation of CAFs, establishing a feed-forward loop that aids in the formation of a permanently stiff tumor niche. It is important to note that CSCs are not distributed uniformly across cancerous tissues. More CSCs are distributed in invasive areas to facilitate metastasis. The invasive tumor front (ITF) is stiffer than the tumor’s core