SMAD2 and cancer: Moreover, dual phosphorylation of pSMAD2/3 in the linker and C-terminal region (pSMAD2/3L+C) are observed in several cancers at the invasion front, while Smad2-deficient fibroblasts from mouse embryos (Smad2−/− MEFs) expressing Smad2 mutants lacking linker serine/threonine (T220V/S245A/S250A/S255A) or C-terminal phosphorylation sites (S464A/S465A/S467A), as well as combinations of both, exhibit reduced infiltration capacity [13].