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Normal and altered Smad4 signaling (A) Canonical TGF-β signaling in normal cells or stromal cells. (B) Smad4 loss in tumor epithelia causes compensatory TGF-β overproduction that signals through Smad2/3 in tumor cells and paracrine TGF-β signaling in stromal cells through Smad2/3/4. TGF-β signaling can be blocked by a TGF-βRI inhibitor.
