Cancers, Vol. 10, Pages 199: TGF-β Sustains Tumor Progression through Biochemical and Mechanical Signal Transduction

Cancers, Vol. 10, Pages 199: TGF-β Sustains Tumor Progression through Biochemical and Mechanical Signal Transduction

Cancers doi: 10.3390/cancers10060199

Authors: Robert L. Furler Douglas F. Nixon Christine A. Brantner Anastas Popratiloff Christel H. Uittenbogaart

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

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