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

Robert L Furler; Douglas F Nixon; Christine A Brantner; Anastas Popratiloff; Christel H Uittenbogaart

doi:10.3390/cancers10060199

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

Cancers (Basel). 2018 Jun 14;10(6):199. doi: 10.3390/cancers10060199.

Authors

Robert L Furler¹, Douglas F Nixon², Christine A Brantner³, Anastas Popratiloff⁴, Christel H Uittenbogaart⁵

Affiliations

¹ Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, 413 E 69th St., Belfer Research Building, New York, NY 10021, USA. rlf2001@med.cornell.edu.
² Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, 413 E 69th St., Belfer Research Building, New York, NY 10021, USA. dnixon@med.cornell.edu.
³ GW Nanofabrication and Imaging Center, Office of the Vice President for Research, George Washington University, Washington, DC 20052, USA. chrisbrantner@gwu.edu.
⁴ GW Nanofabrication and Imaging Center, Office of the Vice President for Research, George Washington University, Washington, DC 20052, USA. anastas@gwu.edu.
⁵ 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. uittenbo@ucla.edu.

Abstract

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.

Keywords: DNA damage; TAK1; TGF-β; cancer; extracellular matrix; immunosuppression; mechanobiology; tensegrity.

Publication types

Review

Abstract

Publication types

Grants and funding