IRS1 and neoplasm: In normal epithelial cells which express TβR‐V, TGF‐β suppresses carcinogenesis by potently inhibiting cell growth via stimulating TβR‐V‐mediated IRS‐2‐dependent tumor suppressor signaling cascade (TβR‐V/IRS‐2/PP1/pRb) in concert with TβR‐I–TβR‐II‐mediated canonical TGF‐β signaling (TβR‐I/TβR‐II/Smad2/3/4) and by suppressing tumor progression via stimulating TβR‐V‐mediated IRS‐1‐dependent activation and formation of PP1‐PP2A complexes (TβR‐V/IRS‐1/PP1‐PP2A) which targets and suppresses TβR‐I‐mediated non‐Smad tumor progression signaling (Figure 8B).