Figure 4.

Hypothetic model showing how integrins may trigger therapy resistance in stiff micro-environmental niches. Therapy-resistant tumors are often characterized by an increase in matrix stiffness. Cancer-associated fibroblast (CAF) integrins (mainly α5β1 integrin) generate mechanical forces that increase ECM protein assembly and matrix rigidity. In cancer cells, the sensing of CAF-generated tension by integrins activates transcriptional co-regulators YAP and TAZ and their translocation to the nucleus. The transcriptional response leads to therapy resistance (adapted from [186]).