FOXM1 induced by E6 oncoprotein promotes tumor invasion and chemoresistance in HPV-infected lung cancer

Induction of FOXM1 expression by E6 oncoprotein via the MZF1/NKX2-1 axis is responsible for soft-agar growth, invasiveness, and stemness in HPV-positive oral and lung cancer cells. Among patients, the presence of HPV16/18 DNA was positively correlated with NKX2-1 and FOXM1 expression in oral and lung tumors. When oral or lung cancer patients were individually divided into four subgroups by two parameters (HPV and FOXM1), HPV-positive oral or lung cancer patients with high-FOXM1 tumors exhibited the worst overall survival and relapse free survival among the four subgroups of both cancers. Xenograft lung tumor nodules in nude mice injected with HPV-positive oral and or lung cancer stable clones were markedly diminished by FOXM1 inhibitor (thiostrepton). Therefore, we suggest that FOXM1 may potentially represent a therapeutic target in HPV-positive oral or and lung cancer patients with HPV16/18-positive tumors.