title: TIMPs: versatile extracellular regulators in cancer.
abstract: A compelling long-term goal of cancer biology is to understand the crucial players during tumorigenesis in order to develop new interventions. Here, we review how the four non-redundant tissue inhibitors of metalloproteinases (TIMPs) regulate the pericellular proteolysis of a vast range of matrix and cell surface proteins, generating simultaneous effects on tumour architecture and cell signalling. Experimental studies demonstrate the contribution of TIMPs to the majority of cancer hallmarks, and human cancers invariably show TIMP deregulation in the tumour or stroma. Of the four TIMPs, TIMP1 overexpression or TIMP3 silencing is consistently associated with cancer progression or poor patient prognosis. Future efforts will align mouse model systems with changes in TIMPs in patients, will delineate protease-independent TIMP function, will pinpoint therapeutic targets within the TIMP-metalloproteinase-substrate network and will use TIMPs in liquid biopsy samples as biomarkers for cancer prognosis.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, TMDT 301-13, 101 College Street, Toronto, Ontario, M5G IL7 Canada.|Bodenmiller Laboratory, University of Zürich, Institute for Molecular Life Sciences, Winterthurstrasse 190, 8057 Zürich, Switzerland.
authors.forename: Hartland W
authors.initials: HW
authors.lastname: Jackson
authors.affiliation: Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, TMDT 301-13, 101 College Street, Toronto, Ontario, M5G IL7 Canada.
authors.forename: Virginie
authors.initials: V
authors.lastname: Defamie
authors.affiliation: Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, TMDT 301-13, 101 College Street, Toronto, Ontario, M5G IL7 Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Waterhouse
authors.affiliation: Department of Medical Biophysics, University of Toronto, Princess Margaret Cancer Centre, TMDT 301-13, 101 College Street, Toronto, Ontario, M5G IL7 Canada.
authors.forename: Rama
authors.initials: R
authors.lastname: Khokha
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000503:physiopathology*; D059748:Proteolysis; D015398:Signal Transduction; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism* / Q000502:physiology; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D019714:Tissue Inhibitor of Metalloproteinases