Human Papillomavirus Type 16/18 Oncoproteins: Potential Therapeutic Targets in Non-smoking Associated Lung Cancer

Abstract

High-risk human papillomavirus (HPV) especially HPV-16 and HPV-18 types are speculated to be important risk factors in non-smoking associated lung cancer in Asia. Increasing evidence has demonstrated that HPV oncoproteins may contribute to lung tumorigenesis and cell transformation. Importantly, HPV 16/18 E6 and E7 oncoproteins can mediate expression of multiple target genes and proteins, such as p53/pRb, VEGF, HIF-1α, cIAP-2, and hTERT, and contribute to cell proliferation, angiogenesis and cell immortalization through different signaling pathways in lung cancer. This article provides an overview of experiment data on HPV-associated lung cancer, describes the main targets on which HPV E6/E7 oncoproteins act, and further discusses the potential signaling pathways in which HPV E6/E7 oncoproteins are involved. In addition, we also raise questions regarding existing problems with the study of HPV-associated lung cancer.

Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells

“…E7 oncoprotein binds with pRb (Zhang and Tang, 2012) and this retinoblastoma protein controls the G1-S transition in the cell cycle. Interaction of pRb and E7 disrupts and releases E2F (Zhang and Tang, 2012).…”

“…E7 oncoprotein binds with pRb (Zhang and Tang, 2012) and this retinoblastoma protein controls the G1-S transition in the cell cycle. Interaction of pRb and E7 disrupts and releases E2F (Zhang and Tang, 2012). pRb recruits HDAC and changes the chromatin structure at the E2F-responsive promoter, thus controls the transcriptional activity of E2F (Tanaki et al, 2004).…”

Involvement of TP53 and TP16 expression in human papillomavirus-associated non-small cell lung cancer

“…In addition, a significant correlation between HPV infection and TP16 expression has been observed in a variety of HPV-associated tumor specimens (17–19). Overexpression of TP16, a cyclin-dependent kinase inhibitor, can prevent the phosphorylation of the retinoblastoma protein, an important cellular tumor suppressor, resulting in its activation and consequent inhibition of cell cycle progression (20). While there is accumulating evidence that the HPV 16/18 E6 oncoprotein is indeed expressed in lung tumors and is involved in TP53 and TP16 signaling, the correlation between HPV infection and the expression of these proteins remains controversial.…”

8-60hIPP5m-Induced G2/M Cell Cycle Arrest Involves Activation of ATM/p53/p21cip1/waf1Pathways and Delayed Cyclin B1 Nuclear Translocation

“…HPV-E6 protein forms a complex with E6-AP and subsequently interacts with p53, leading to ubiquitin dependent proteasomal degradation (Subramanian and Chinnappan, 2013). E7 oncoprotein binds with pRb which controls the G1-S transition in cell cycle (Zhang and Tang, 2012).…”