MMP24 as a Target of YAP Is a Potential Prognostic Factor in Cancer Patients

Abstract

The extracellular matrix (ECM) surrounding cancer cells becomes stiffer during tumor progression, which influences cancer cell behaviors such as invasion and proliferation through modulation of gene expression as well as remodeling of the actin cytoskeleton. In this study, we show that MMP24 encoding matrix metalloproteinase (MMP)-24 is a novel target gene of Yes-associated protein (YAP), a transcription coactivator known as a mechanotransducer. We first examined the effect of substrate stiffness on MMP24 expression in MCF-7 human breast cancer cells and showed that the expression of MMP24 was significantly higher in cells grown on stiff substrates than that on soft substrates. The MMP24 expression was significantly reduced by knockdown of YAP. In contrast, the expression of constitutively active YAP increased MMP24 promoter activity. In addition, binding of YAP to the MMP24 promoter was confirmed by the chromatin immunoprecipitation (ChIP) assay. These results show that ECM stiffening promotes YAP activation, thereby inducing MMP24 expression. Based on the Human Protein Atlas database, breast cancer patients with lower MMP24 expression exhibit the worse survival rates overall. Thus, MMP24 may negatively regulate the aggressiveness of cancer cells under the stiff ECM environment during tumor progression.

CeRNA Network Analysis Representing Characteristics of Different Tumor Environments Based on 1p/19q Codeletion in Oligodendrogliomas

“…The invasion process of cancer involves the degradation of these ECM components by matrix metalloproteinases (MMP) as well [74]. MMP24 is a gene encoding matrix metalloproteinase-24 and has recently been reported to negatively regulate the aggressiveness of cancer cells in breast cancer as a target gene of yes-associated protein (YAP) [75].…”

The immunomodulatory role of matrix metalloproteinases in colitis-associated cancer

“…The final member of the MMPs family discussed here is MT-MMPs, which are an important mediator of infiltration. The influence of MT-MMPs on pathological process is mainly reflected in their promotion of tumor invasion ( 140 , 155 – 161 , 165 , 166 ). The ability to activate MMP-2 is one of the reasons why most MT-MMPs play these roles ( 173 ).…”