Project name: Mus musculus

Description: Cancer metastasis remains an important unsolved problem. Matrix metalloproteinases (MMPs) have been shown to promote cancer cell transformation, migration, invasion, and metastasis through alteration of the extracellular microenvironment, and alter intracellular signaling and genome status. In addition, recent studies have shown intracellular and intranuclear localization, as well as roles of MMPs. In the present study, we examined gene expression signatures of high- and low-metastatic mouse colon cancer cells, and found that Mmp3 was expressed at the highest level in the high-metastatic cells. Profound nuclear localization of Mmps was found in primary explant sites as well as in areas of metastasis in lungs. In addition to the native 50-kDa Mmp3, a short 25-kDa PEX domain and active Mmp3 dimer were found in metastatic cancer cells, indicating novel roles for these forms. Knockdown of Mmp3 attenuated cancer cell viability, migration, and invasion in vitro, along with metastasis in an in vivo transplantation model, as well as cancer cell migration and invasion. These findings suggest that MMPs including intracellular, short, and dimerized forms are involved with malignant progression of cancer, thus they may be suitable as biomarkers and therapeutic targets.Overall design: We analyzed gene expression signature of the highly evolved LuM1 as compared to that in the non-metastatic NM11 and the parental colon26 cells.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Last updated: 2017-03-29