Overexpression of human papillomavirus (HPV) type 16 oncoproteins promotes angiogenesis via enhancing HIF-1α and VEGF expression in non-small cell lung cancer cells

HPV-16 infection may play an important role in the development of non-small cell lung cancer (NSCLC) among never-smokers. Due to the critical role of angiogenesis in NSCLC development, we describe here the effect of HPV-16 oncoproteins on angiogenesis in NSCLC and the underlying mechanisms. We found that overexpression of HPV-16 E6 and E7 oncoproteins in NSCLC cells significantly promoted angiogenesis both in vitro and in vivo, and correspondingly, an enhanced expression of HIF-1α and VEGF, important pro-angiogenic factors in tumor angiogenesis. Meanwhile, overexpression of HPV-16 oncoproteins also led to HIF-1α-dependent increases in the secretion of several other pro-angiogenic factors, including IL-8. Our findings suggest that HPV-16 oncoproteins contribute to the development of NSCLC possibly by promoting HIF-1α/VEGF-mediated tumor angiogenesis.

► Overexpression of HPV-16 oncoproteins in NSCLC cells promoted angiogenesis. ► Overexpression of HPV-16 oncoproteins enhanced HIF-1α protein accumulation. ► Overexpression of HPV-16 oncoproteins increased VEGF protein and mRNA expression. ► HPV-16 oncoproteins-induced VEGF and IL-8 expression was HIF-1α-dependent.