Once a cancer has spread to other sites in the body, this aggressive, metastatic cancer is extremely refractory to most treatment options. Dr. Jonathan Kurie and coworkers at M.D. Anderson Cancer Center in Houston, Texas wanted to better understand the molecular pathways that underlie metastasis. They examined a known promoter of metastasis, a gene transcription factor known as ZEB1 that regulates the expression of multiple regulatory microRNAs. The team specifically studied which microRNAs regulated by ZEB1 contributed to its metastasis-promoting functions. They found that a major target of ZEB1 is microRNA-34a (miR34-a). Forced expression of miR-34a decreased tumor cell invasion and metastasis in mice, and expression patterns of miR-34a in human lung adenocarcinomas predicted clinical outcome. Their results suggest that pharmaceuticals targeting miR-34a may merit exploration as a therapeutic agent in lung cancer patients.
TITLE: ZEB1 drives prometastatic actin cytoskeletal remodeling by downregulating miR-34a expression