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Tissue inhibitor of metalloproteinase-1 promotes cell proliferation through YAP/TAZ activation in cancer
- Source :
- Oncogene; January 2018, Vol. 37 Issue: 2 p263-270, 8p
- Publication Year :
- 2018
-
Abstract
- Tissue inhibitor of metalloproteinase-1 (TIMP-1), a member of the TIMP family (TIMP-1 to 4), is highly expressed in various types of cancer and forms a complex with its receptor CD63 and Integrin β1. However, the precise oncogenic mechanism of TIMP-1 remains unclear. Yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) are transcription co-activators enhancing the transcription of specific genes related to cell proliferation. But the mechanism of aberrant YAP/TAZ activation in cancer is not fully understood. Here, we showed that TIMP-1 activates YAP/TAZ as novel downstream targets to promote cell proliferation. The TIMP-1-CD63-Integrin β1 axis activates Src and promotes RhoA-mediated F-actin assembly, leading to LATS1/2 inactivation. This results in under-phosphorylation, protein stabilization and nuclear translocation of YAP/TAZ (YAP/TAZ activation); CTGF production; and cell proliferation. Furthermore, the TIMP-1-YAP/TAZ axis is aberrantly activated in various types of cancer cells or tissues. TIMP-1 knockdown inhibits cell proliferation through YAP/TAZ inactivation in cancer cells. This study found that TIMP-1 accelerates cell proliferation through YAP/TAZ activation in cancer, and suggests the TIMP-1-YAP/TAZ axis may be a novel potential drug target for cancer patients.
Details
- Language :
- English
- ISSN :
- 09509232 and 14765594
- Volume :
- 37
- Issue :
- 2
- Database :
- Supplemental Index
- Journal :
- Oncogene
- Publication Type :
- Periodical
- Accession number :
- ejs44414458
- Full Text :
- https://doi.org/10.1038/onc.2017.321