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Publication : TIMPs: versatile extracellular regulators in cancer.

First Author  Jackson HW Year  2017
Journal  Nat Rev Cancer Volume  17
Issue  1 Pages  38-53
PubMed ID  27932800 Mgi Jnum  J:239315
Mgi Id  MGI:5828322 Doi  10.1038/nrc.2016.115
Citation  Jackson HW, et al. (2017) TIMPs: versatile extracellular regulators in cancer. Nat Rev Cancer 17(1):38-53
abstractText  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.
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