TIMPs as Extracellular Regulators of Cancer: From Tumour Biology to Liquid Biopsy Biomarkers
This Nature Reviews Cancer article examines the four tissue inhibitors of metalloproteinases and their roles in regulating pericellular proteolysis during tumour progression. TIMP1 overexpression and TIMP3 silencing consistently associate with poor prognosis across human cancers. The authors propose that TIMPs in liquid biopsy specimens could serve as prognostic biomarkers, and call for future work to delineate protease-independent TIMP functions and identify therapeutic targets within the TIMP-metalloproteinase network.
The original study
TIMPs: versatile extracellular regulators in cancer.
- Authors
- Jackson HW, Defamie V, Waterhouse P, Khokha R
- Journal
- Nature reviews. Cancer
- Type
- Journal Article, Review
- PMID
- 27932800
Original 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.