MAPK8 and neoplasm: Thus, the stiffness of the adhesive substrate correlates with the expression of lysyl oxidases, especially LOXL2 in hepatocarcinoma cells, which could be attributed to the activation of the integrin β1/α5/JNK/c-JUN signalling pathway in these cells.[88] Increased ECM strength has a similar effect on the expression of LOX in tumour-associated fibroblasts.[30] Accordingly, lysyl oxidase activity and integrin signalling pathways mutually reinforce each other in the sense of a positive-feedback loop, and mechanical stiffening of the ECM contributes significantly to tumour malignancy.[30,89]