TY - JOUR
T1 - Matrix metalloproteinases in stem cell regulation and cancer
AU - Kessenbrock, Kai
AU - Wang, Chih Yang
AU - Werb, Zena
N1 - Funding Information:
Supported by funds from the National Cancer Institute ( R01 CA57621 to Z.W. and K99 CA181490 to K.K.). Chih-Yang Wang is supported by a grant from the National Science Council , Taiwan ( NSC-102-2922-I-006-362 ).
Publisher Copyright:
© 2015.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Since Gross and Lapiere firstly discovered matrix metalloproteinases (MMPs) as important collagenolytic enzymes during amphibian tadpole morphogenesis in 1962, this intriguing family of extracellular proteinases has been implicated in various processes of developmental biology. However, the pathogenic roles of MMPs in human diseases such as cancer have also garnered widespread attention. The most straightforward explanation for their role in cancer is that MMPs, through extracellular matrix degradation, pave the way for tumor cell invasion and metastasis. While this notion may be true for many circumstances, we now know that, depending on the context, MMPs may employ additional modes of functionality. Here, we will give an update on the function of MMPs in development and cancer, which may directly regulate signaling pathways that control tissue homeostasis and may even work in a non-proteolytic manner. These novel findings about the functionality of MMPs have important implications for MMP inhibitor design and may allow us to revisit MMPs as drug targets in the context of cancer and other diseases.
AB - Since Gross and Lapiere firstly discovered matrix metalloproteinases (MMPs) as important collagenolytic enzymes during amphibian tadpole morphogenesis in 1962, this intriguing family of extracellular proteinases has been implicated in various processes of developmental biology. However, the pathogenic roles of MMPs in human diseases such as cancer have also garnered widespread attention. The most straightforward explanation for their role in cancer is that MMPs, through extracellular matrix degradation, pave the way for tumor cell invasion and metastasis. While this notion may be true for many circumstances, we now know that, depending on the context, MMPs may employ additional modes of functionality. Here, we will give an update on the function of MMPs in development and cancer, which may directly regulate signaling pathways that control tissue homeostasis and may even work in a non-proteolytic manner. These novel findings about the functionality of MMPs have important implications for MMP inhibitor design and may allow us to revisit MMPs as drug targets in the context of cancer and other diseases.
KW - Cancer
KW - Cell differentiation
KW - Hemopexin domain
KW - Invasion
KW - Stem cell niche
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U2 - 10.1016/j.matbio.2015.01.022
DO - 10.1016/j.matbio.2015.01.022
M3 - Review article
C2 - 25661772
AN - SCOPUS:84930763579
VL - 44-46
SP - 184
EP - 190
JO - Matrix Biology
JF - Matrix Biology
SN - 0945-053X
ER -