ERK Signaling Pathway Is Involved in HPV-16 E6 but not E7 Oncoprotein-Induced HIF-1α Protein Accumulation in NSCLC Cells

作者：Liu, Fei; Lin, Bihua; Liu, Xin; Zhang, Wenzhang; Zhang, Erying; Hu, Liang; Ma, Yuefan; Li, Xiangyong; Tang, Xudong^*

来源：Oncology Research, 2016, 23(3): 109-118.

DOI：10.3727/096504015X14496932933610

• Extracellular signal-regulated kinases (ERK) 1/2
• Human papillomavirus
• Non-small cell lung cancer
• Angiogenesis
• Hypoxia-inducible factor-1 alpha
• Vascular endothelial growth factor (VEGF)
• Interleukin-8

Extracellular signal-regulated kinase (ERK)1/2 signaling pathway plays a critical role in regulating tumor angiogenesis. Our previous studies have demonstrated that HPV-16 oncoproteins enhanced hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein accumulation and vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) expression in non-small cell lung cancer (NSCLC) cells, thus contributing to angiogenesis. In this study, we further investigated the role of ERK1/2 signaling pathway in HPV-16 oncoprotein-induced HIF-1 alpha, VEGF, and IL-8 expression and in vitro angiogenesis in NSCLC cells. Our results showed that HPV-16 E6 and HPV-16 E7 oncoproteins promoted the activation of ERK1/2 signaling pathway in A549 and NCI-H460 cells. Moreover, PD98059, a specific inhibitor of ERK1/2, blocked in vitro angiogenesis stimulated by HPV-16 E6 but not E7 oncoprotein. Additionally, HIF-1 alpha protein accumulation and VEGF and IL-8 expression in NSCLC cells induced by HPV-16 E6 but not E7 oncoprotein were significantly inhibited by PD98059. Taken together, our results suggest that ERK1/2 signaling pathway is involved in HPV-16 E6 but not E7 oncoprotein-induced HIF-1 alpha, VEGF, and IL-8 expression in NSCLC cells, leading to the enhanced angiogenesis in vitro.

• 出版日期2016
• 单位广东医科大学