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Mislocalization and unconventional functions of cellular MMPs in cancer

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Abstract

MMPs are multifunctional enzymes capable of targeting the extracellular matrix, growth factors, cytokines and cell surface-associated adhesion and signaling receptors. The cellular localization and the activity of MMPs are tightly controlled at both the transcriptional and the post-transcriptional levels. Mislocalization and presentation in unconventional cellular compartments provide MMPs with an opportunity to cleave previously unidentified proteins. This review is focused on two, entirely different MMPs, one of which is membrane-tethered and another of which is soluble (MT1-MMP and MMP-26, respectively) from twenty four known human MMPs. Our recent studies determined that both of these enzymes functioned at unexpected cellular compartments and it was resulted in the identification of novel proteolytic pathways, whose significance we only partially comprehend as of this writing. It is reasonable, however, to hypothesize from these data that many individual MMPs perform in a similar manner and display a much broader range of functions compared to what we earlier thought.

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Abbreviations

CT:

cytoplasmic tail

DCIS:

ductal carcinoma in situ

ERα anf ERβ:

estrogen receptor-α and -β, respectively

ECM:

extracellular matrix

ERE:

estrogen response element

GFP:

green fluorescent protein

MMP:

matrix metalloproteinase

MT1-, MT2-, MT3-, MT4-, MT5- and MT6-MMP:

membrane type-1, -2, -3, -4, -5 and -6 matrix metalloproteinase, respectively

siRNA:

small interfering RNA

TIMP:

tissue inhibitor of matrix metalloproteinases

VEGF:

vascular endothelial growth factor

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    Alex Y. Strongin

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Strongin, A.Y. Mislocalization and unconventional functions of cellular MMPs in cancer. Cancer Metastasis Rev 25, 87–98 (2006). https://doi.org/10.1007/s10555-006-7892-y

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