A regulatory BMI 1/let‐7i/ ERK 3 pathway controls the motility of head and neck cancer cells

Extracellular signal‐regulated kinase 3 ( ERK 3) is an atypical mitogen‐activated protein kinase ( MAPK ), whose biological activity is tightly regulated by its cellular abundance. Recent studies have revealed that ERK 3 is upregulated in multiple cancers and promotes cancer cell migration/invasion and drug resistance. Little is known, however, about how ERK 3 expression level is upregulated in cancers. Here, we have identified the oncogenic polycomb group protein BMI 1 as a positive regulator of ERK 3 level in head and neck cancer cells. Mechanistically, BMI 1 upregulates ERK 3 expression by suppressing the tumor suppressive micro RNA (mi RNA ) let‐7i, which directly targets ERK 3 mRNA . ERK 3 then acts as an important downstream mediator of BMI 1 in promoting cancer cell migration. Importantly, ERK 3 protein level is positively correlated with BMI 1 level in head and neck tumor specimens of human patients. Taken together, our study revealed a molecular pathway consisting of BMI 1, mi RNA let‐7i, and ERK 3, which controls the migration of head and neck cancer cells, and suggests that ERK 3 kinase is a potential new therapeutic target in head and neck cancers, particularly those with BMI 1 overexpression.