The oncogenic signalling pathways of the identified extra cellular matrix proteins are (a) caveolin-1: PI3K/AKT and Ras/Raf signaling through the ERK; (b) Desmin: PI3K/AKT through caspase; (c) microfibril associated glycoprotein 4: ERK/MMP signalling through FAK and c-Jun; (d) collagen α-1: FAK signalling through PI3K/AKT and MAPK/ERK, and (e) fibrillin 1: SMAD2/3/4 and MEK pathway through ERK; which induces cell proliferation, survival, motility, angiogenesis, hypoxia, cancer stem cell activity, epithelial to mesenchymal transition and eventually lymph node metastasis105–109. This evidence concerns the gene SMAD2 and cancer.