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

1
Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, 413 E 69th St., Belfer Research Building, New York, NY 10021, USA
2
GW Nanofabrication and Imaging Center, Office of the Vice President for Research, George Washington University, Washington, DC 20052, USA
3
Departments of Microbiology, Immunology and Molecular Genetics, Medicine, Pediatrics, UCLA AIDS Institute and the Jonsson Comprehensive Cancer Center, University of California, 615 Charles E. Young Drive South, BSRB2, Los Angeles, CA 90095, USA
*
Author to whom correspondence should be addressed.
Cancers 2018, 10(6), 199; https://doi.org/10.3390/cancers10060199
Received: 24 May 2018 / Revised: 12 June 2018 / Accepted: 12 June 2018 / Published: 14 June 2018
(This article belongs to the Special Issue TGF-Beta Signaling in Cancer)
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. View Full-Text
Keywords: TGF-β; cancer; immunosuppression; TAK1; mechanobiology; extracellular matrix; tensegrity; DNA damage TGF-β; cancer; immunosuppression; TAK1; mechanobiology; extracellular matrix; tensegrity; DNA damage
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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.

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