TGF-β Sustains Tumor Progression through Biochemical and Mechanical Signal Transduction

Transforming growth factor beta (TGF-beta) signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD transcription factor signaling, TGF-beta can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix (ECM) remodeling. In this article, we review how TGF-beta activated kinase 1 (TAK1) activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-beta receptors. Additionally, we discuss the role of TGF-beta in the mechanobiology of cancer. Understanding how TGF-beta dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development is critical for designing therapeutics that inhibit tumor progression while bolstering the immune response.