Furler, R.L.; Nixon, D.F.; Brantner, C.A.; Popratiloff, A.; Uittenbogaart, C.H. TGF-β Sustains Tumor Progression through Biochemical and Mechanical Signal Transduction. Cancers2018, 10, 199.
Furler, R.L.; Nixon, D.F.; Brantner, C.A.; Popratiloff, A.; Uittenbogaart, C.H. TGF-β Sustains Tumor Progression through Biochemical and Mechanical Signal Transduction. Cancers 2018, 10, 199.
TGF-β signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix remodeling. In this article, we will review how TAK1 activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we will discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development will be critical in designing therapeutics which inhibit tumor progression while bolstering the immune response.
TGF-β; cancer; immunosuppression; TAK1; mechanobiology; extracellular matrix; tensegrity; DNA damage
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